jimnoneill/paper-to-field-training huggingface dataset:
Data from Small-Molecule Sigma1 Modulator Induces Autophagic Degradation of PD-L1

&lt;div&gt;Abstract&lt;p&gt;Emerging evidence suggests that Sigma1 (&lt;i&gt;SIGMAR1&lt;/i&gt;, also known as sigma-1 receptor) is a unique ligand-regulated integral membrane scaffolding protein that contributes to cellular protein and lipid homeostasis. Previously, we demonstrated that some small-molecule modulators of Sigma1 alter endoplasmic reticulum (ER)–associated protein homeostasis pathways in cancer cells, including the unfolded protein response and autophagy. Programmed death-ligand 1 (PD-L1) is a type I integral membrane glycoprotein that is cotranslationally inserted into the ER and is processed and transported through the secretory pathway. Once at the surface of cancer cells, PD-L1 acts as a T-cell inhibitory checkpoint molecule and suppresses antitumor immunity. Here, we demonstrate that in Sigma1-expressing triple-negative breast and androgen-independent prostate cancer cells, PD-L1 protein levels were suppressed by RNAi knockdown of Sigma1 and by small-molecule inhibition of Sigma1. Sigma1-mediated action was confirmed by pharmacologic competition between Sigma1-selective inhibitor and activator ligands. When administered alone, the Sigma1 inhibitor decreased cell surface PD-L1 expression and suppressed functional interaction of PD-1 and PD-L1 in a coculture of T cells and cancer cells. Conversely, the Sigma1 activator increased PD-L1 cell surface expression, demonstrating the ability to positively and negatively modulate Sigma1 associated PD-L1 processing. We discovered that the Sigma1 inhibitor induced degradation of PD-L1 via autophagy, by a mechanism distinct from bulk macroautophagy or general ER stress–associated autophagy. Finally, the Sigma1 inhibitor suppressed IFNγ-induced PD-L1. Our data demonstrate that small-molecule Sigma1 modulators can be used to regulate PD-L1 in cancer cells and trigger its degradation by selective autophagy.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Implications:&lt;/b&gt; Sigma1 modulators sequester and eliminate PD-L1 by autophagy, thus preventing functional PD-L1 expression at the cell surface. This posits Sigma1 modulators as novel therapeutic agents in PD-L1/PD-1 blockade strategies that regulate the tumor immune microenvironment.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Visual Overview:&lt;/b&gt; &lt;a href="http://mcr.aacrjournals.org/content/molcanres/16/2/243/F1.large.jpg" target="_blank"&gt;http://mcr.aacrjournals.org/content/molcanres/16/2/243/F1.large.jpg&lt;/a&gt;. &lt;i&gt;Mol Cancer Res; 16(2); 243–55. ©2017 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;

Topic: Pharmacological Receptor Mechanisms and Effects
Subfield: Molecular Biology
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences
USAF Bioenvironmental Noise Data Handbook. Volume 118. MD-4 Generator.

The MD-4 Generator is a motor driven generator set designed to furnish alternating current for hangers, maintenance shops and industrial facilities where precision bench mockup and test equipment requiring precise power are operated and tested. This report provides measured data defining the bioacoustic environments produced by this unit operating inside a large aircraft hanger at normal rated conditions. Near-field data are reported for 37 locations in a wide variety of physical and psychoacoustic measures: overall and band sound pressure levels, C-weighted and A-weighted sound levels, preferred speech interference level, perceived noise level, and limiting times for total daily exposure of personnel with and without standard Air Force ear protectors.

Topic: Noise Effects and Management
Subfield: Speech and Hearing
Field: Health Professions
Domain: Health Sciences
IDDF2024-ABS-0229 Early diagnosis and prognosis prediction of gastric cancer by high-performance serum lipidome fingerprints: a multi-cohort study

<h3>Background</h3> Early detection is warranted to improve the prognosis of gastric cancer (GC), but it remains challenging. Liquid biopsy combined with machine learning will provide new insights into the diagnostic strategies of GC. Lipid metabolism reprogramming plays a crucial role in the initiation and development of tumors. Therefore, we aimed to map the lipid metabolism landscape of GC and develop novel lipid-based tools of liquid biopsy for early diagnosis and risk stratification of GC. <h3>Methods</h3> This cohort study enrolled 944 participants, including 440 patients with GC, 71 patients with gastric precancerous lesions and 433 healthy donors (IDDF2024-ABS-0229 Figure 1. Study design). Based on the lipid detection of the serums from participants by ultra-performance liquid chromatography-mass spectrometry, the serum lipid metabolic landscape of GC was depicted. Linear discriminant analysis and clustering analysis were employed to establish and validate the serum lipid metabolic signature (SLMS) and the gastric cancer prognostic subtype (GCPS), which were applied for the diagnosis and prognosis prediction of GC, respectively. Besides, multi-omics analysis was performed to further interpret the lipid metabolism disturbance in GC tissues and demonstrate the reliability of SLMS and GCPS. <h3>Results</h3> The SLMS, consisting of 19 lipids (IDDF2024-ABS-0229 Figure 2. 19 lipids in the serum lipid metabolic signature), showed excellent performances in discriminating between GC patients and healthy donors (training cohort, AUC=0.993; testing cohort, AUC=0.989; external validation cohort, AUC=0.965; predictive cohort, AUC=0.978; (IDDF2024-ABS-0229 Figure 3. The diagnostic performance of SLMS in identifying GC)). Importantly, the SLMS could efficiently distinguish early-stage GC (stage I/II) patients from healthy donors (training cohort, AUC=0.992; testing cohort, AUC=0.996; external cohort, AUC=0.975; predictive cohort, AUC=0.963; (IDDF2024-ABS-0229 Figure 4. The efficacy of SLMS in diagnosing early SATGE GE)). Moreover, the GCPS effectively predicted high-risk GC patients with poor overall survival, especially patients with advanced GC (stage III/IV, (IDDF2024-ABS-0229 Figure 5. The GCPS can predict the survival of GC patients)). Finally, the alteration of lipid metabolism in GC and the metabolic heterogeneity between two prognostic subtypes were verified in situ while some potential gene targets for GCPS were identified (IDDF2024-ABS-0229 Figure 6. Multi-omics revealed the lipid metabolism disturbance in GC). <h3>Conclusions</h3> Lipid metabolic reprogramming arose along with the development of gastric cancer. We could efficiently screen GC patients and predict their survival through the SLMS and GCPS.

Topic: Cancer, Lipids, and Metabolism
Subfield: Cancer Research
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences
The influence of selected factors on the failure rate of the water pipelines located on t he area of the impact of mining tremors

The article presents the influence of the selected factors, including mining tremors, described by the parameter PGVHmax on the failure rate of the water distribution pipelines. In created multiple regression models, the following independent variables were used: diameter and material from which the pipes were made, operation time without failure, the age of pipes, the value of pressure and PGVHmax. The values of PGVHmax in places with damaged water pipelines were determined by constructed the seismic wave propagation models. The analysis was carried out for a random sample of all water pipelines and extracted from this sample new groups: steel and gray cast iron pipes, their diameters, diameters and materials, and their construction time.

Topic: Water Systems and Optimization
Subfield: Civil and Structural Engineering
Field: Engineering
Domain: Physical Sciences
Implicit Racial Associations Among Academic Physiatrists and Trainees

Abstract This study investigated the prevalence of implicit racial associations among academic physiatrists and trainees. We administered the Harvard Implicit Association Test on race (Black/White) to 71 participants from a national academic physiatry association. The survey gathered demographic data (age, gender, ethnicity, race, professional role, and years of experience) and Harvard Implicit Association Test results, where participants reported a preference for Black race, White race, or no race preference. The majority of respondents (54.5%) displayed a preference for White race, with regression analysis revealing that participant race was the only significant predictor of this bias ( P = 0.03), No associations were found between age, gender, ethnicity, or trainee status and the Harvard Implicit Association Test results. The results indicated a significant pattern of implicit bias favoring White race among academic physiatrists and trainees, consistent with findings in other medical fields. The study emphases the need for ongoing efforts to be aware of and manage implicit biases in the field of physician medicine and rehabilitation, aiming to enhance patient outcomes and reduce healthcare disparities.

Topic: Diversity and Career in Medicine
Subfield: Gender Studies
Field: Social Sciences
Domain: Social Sciences
Comparison of adults with attention-deficit/hyperactivity disorder versus Asperger’s disorder using the WAIS-R

Objective: The present study compared results on the Wechsler Adult Intelligence Scale-Revised (WAIS-R) among adult patients with attention-deficit/hyperactivity disorder (AD/HD) and those with Asperger’s disorder (AD). Method: WAIS-R results were compared between 16 adults with AD/HD (8 men and 8 women; mean age, 33.81 years; mean full-scale IQ, 101.5) and 15 adults with AD (12 men and 3 women; mean age, 30.93 years; mean full-scale IQ, 104.6). Results: Verbal IQ was significantly higher than performance IQ in the AD group. Among various subtests, scores were the highest for similarities in the AD/HD group and for block design in the AD group. Picture completion test scores were the lowest scores obtained in both groups. A comparison of subtest scores between the AD/HD and AD groups showed scores for information to be significantly higher in the AD group than in the AD/HD group. Conclusions: Our results suggest that there are no differences in verbal IQ, performance IQ, and full-scale IQ scores (except for scores on the information subtest) among adult patients with AD/HD compared with adult patients with AD.

Topic: Autism Spectrum Disorder Research
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
6 Pediatric Obstructive Sleep Apnea

Pediatric obstructive sleep apnea (OSA) is a childhood disorder in which there is upper airway dysfunction causing complete or partial airway obstruction during sleep leading to decreased oxygen saturation or arousals from sleep. It can have dramatic effects on childhood behavior, neurodevelopment, metabolism, and overall health. Early recognition, evaluation, and treatment are important to prevent long-term consequences.

Topic: Obstructive Sleep Apnea Research
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
A note on Thom classes in general cohomology

This note is dedicated to the second author’s teacher, Professor Atsuo Komatsu, in celebration of his seventieth birthday. It is well known [4], [7] that the theory of characteristic classes in general cohomology is essentially based upon one theorem, the Leray-Hirsch Theorem. We further claim [8] that the entire theory could be developed merely from the Künneth Formula if under suitable conditions a truly relative version of the Meyer-Vietoris sequence exists in the general cohomology theory. In his lectures delivered at Aarhus in 1968, Dold [6] set up the necessary machinery including the Leray-Hirsch Theorem to define Chern Classes with values in general cohomology. However, he then stated [6, p. 47] that he “found a difficulty here in choosing adequate orientations (Thorn Classes) for the bundles involved”, and proceeded differently, discarding the “classical” approach used in both ordinary cohomology [9] and K -theory [3]. Later, he [7] published a more categorical work, although the approach to Chern Classes was basically unchanged from his previous work. Consequently, the possibility of the classical direct approach to the theory has remained open.

Topic: Homotopy and Cohomology in Algebraic Topology
Subfield: Mathematical Physics
Field: Mathematics
Domain: Physical Sciences
Computing zeta functions of nondegenerate curves

We present a &lt;it&gt;p&lt;/it&gt;-adic algorithm to compute the zeta function of a nondegenerate curve over a finite field using Monsky-Washnitzer cohomology. The paper vastly generalizes previous work since in practice all known cases, for example, hyperelliptic, superelliptic, and &lt;it&gt;C&lt;inf&gt;ab&lt;/inf&gt;&lt;/it&gt; curves, can be transformed to fit the nondegenerate case. For curves with a fixed Newton polytope, the property of being nondegenerate is generic, so that the algorithm works for almost all curves with given Newton polytope. For a genus &lt;it&gt;g&lt;/it&gt; curve over &lt;it&gt;F&lt;/it&gt;&lt;inf&gt;&lt;it&gt;p&lt;/it&gt;&lt;it&gt;n&lt;/it&gt;&lt;/inf&gt;, the expected running time is &lt;it&gt;Õ&lt;/it&gt;(&lt;it&gt;n&lt;/it&gt;3&lt;it&gt;g&lt;/it&gt;6 + &lt;it&gt;n&lt;/it&gt;2&lt;it&gt;g&lt;/it&gt;6.5), whereas the space complexity amounts to &lt;it&gt;Õ&lt;/it&gt;(&lt;it&gt;n&lt;/it&gt;3&lt;it&gt;g&lt;/it&gt;4), assuming &lt;it&gt;p&lt;/it&gt; is fixed.

Topic: Algebraic Geometry and Number Theory
Subfield: Geometry and Topology
Field: Mathematics
Domain: Physical Sciences
The itinerant oscillator model of liquids

A stochastic model for the evaluation of the classical velocity autocorrelation function of an atom in a simple liquid is derived. It is shown that in the harmonic approximation the mean frequency of the thermal vibration ω0 can be expressed in terms of the pair potential and the pair correlation function. The calculated value of ω0 for liquid argon is in excellent agreement with the value found from a comparison of the theoretical velocity spectrum with one obtained recently from a Monte Carlo calculation. The velocity spectra of a methane molecule and of a hydrogen molecule in liquid argon are calculated to aid in the interpretation of recent neutron scattering experiments. The calculation of the scattering cross sections will be given in a separate paper.

Topic: Spectroscopy and Quantum Chemical Studies
Subfield: Atomic and Molecular Physics, and Optics
Field: Physics and Astronomy
Domain: Physical Sciences
Design solutions for pavements structure affected by static and impact load

Pavements of aprons, container and logistic terminals, areas of storage, parking lots, areas of waste utilization are affected by high pressure static and impact loads. These loads strongly influence pavement performance by causing permanent deformations and distresses in the surface and even sometimes pavement failure in the beginning of pavement service. The types of structure, materials and layer thicknesses are the main factors relative to pavement performance. In order to correctly understand the particularity of static and impact loading, distresses of pavement structures affected by such load are emphasized, the load specification and climatic conditions influencing pavement performance are characterized. After analysis of the best practise, the flow chart of pavement structure design model was introduced. The paper gives reasonable pavement type and thickness determination dependent on object of application pavement structure.

Topic: Simulation and Modeling Applications
Subfield: Control and Systems Engineering
Field: Engineering
Domain: Physical Sciences
Facility location and capacity acquisition: An integrated approach

The facility location and capacity acquisition decisions are intertwined, especially within the international context where capacity acquisition costs are location dependent. A review of the relevant literature however, reveals that the facility location and the capacity acquisition problems have been dealt with separately. Thus, an integrated approach for simultaneous optimization of these strategic decisions is presented. Analytical properties of the arising model are investigated and an algorithm for solving the problem is devised. Encouraging computational results are reported. © 1995 John Wiley & Sons, Inc.

Topic: Facility Location and Emergency Management
Subfield: Organizational Behavior and Human Resource Management
Field: Business, Management and Accounting
Domain: Social Sciences
The Effect of Ancylostoma Caninum Infection on Erythropoiesis in Dogs

SummaryRadioactive tracer technics were used to study erythropoietic activity in dogs infected with Ancylostoma caninum. Uninfected animals served as controls. The erythropoietic response of these dogs was evaluated by means of the rate of removal of 59Fe from the plasma and its incorporation into the red blood cells. Results revealed that in infected animals erythropoiesis was either stimulated or remained within the upper limits of normal with the exception of one animal. Under the conditions of these experiments, there was no depression of bone marrow activity. Erythropoietic activity was stimulated to a degree that compensated for the blood loss due to the hookworms. Red cells were being lost from the infected animals by a process other than aging, but none of the animals became grossly anemic. The validity of this method of studying the causes of the anemia associated with hookworm infections is discussed.

Topic: Iron Metabolism and Disorders
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Fabrication process for tall, sharp, hollow, high aspect ratio polymer microneedles on a platform

This paper reports on a new lithographic process for fabricating arrays of tall, high aspect ratio (defined as height/wall thickness), hollow, polymer microneedles on a platform. The microneedles feature a high sharpness (down to 3 µm tip radius) and aspect ratio (>65) which is a factor 2 and 4 better than the state of the art, respectively. The maximum achievable needle shaft length is over 1 mm. The improved performance was obtained by using an anisotropically patterned silicon substrate covered with an antireflective layer as mold for the needle tip and an optimized SU-8 lithographic process. Furthermore, a platform containing liquid feedthroughs holding an arbitrary number of needles out of plane can be manufactured with only one additional process step. The high aspect ratio microneedles undergo failure at the critical load of around 230 mN in case of 1 mm long hollow needles with triangular cross-section and a base of 175 µm. Penetration into human skin is demonstrated as well.

Topic: Advancements in Transdermal Drug Delivery
Subfield: Pharmaceutical Science
Field: Pharmacology, Toxicology and Pharmaceutics
Domain: Life Sciences
Dipolar interaction and demagnetizing effects in magnetic nanoparticle dispersions: Introducing the mean-field interacting superparamagnet model

A model is developed with the aim of analyzing interacting superparamagnets.\nModel is built from magnetic dipolar interaction and demagnetizing mean field\nconcepts. A useful expression for effective demagnetizing factors is achieved,\nwhich allows for the analysis of non uniform spatial distributions of\nnanoparticles. This expression is a function of demagnetizing factors\nassociated with specimen and clusters shapes, and of the mean distances between\nnear neighbor nanoparticles and between clusters, relative to the\ncharacteristic sizes of each of these two types of objects, respectively. It\nexplains effects of magnetic dipolar interactions such as the observation of\napparent nanoparticle magnetic-moments smaller than real ones. It is shown that\nby performing a minimum set of experimental determinations, model application\nallows retrieval of intrinsic properties, like magnetic moment and\nsusceptibility in the absence of interactions. It also permits the estimation\nof mean interparticle and intercluster relative distances, and of demagnetizing\nfactors associated with clusters shape. An expression for magnetic dipolar\nenergy per nanoparticle is also derived. Model experimental test was performed\nby analysis of results reported in the literature and of original results. They\ncorrespond to magnetite particles dispersed in PEGDA-600 polymer, and in PVA\nferrogels. Experimental results display different magnetic response when prism\nshaped specimens are measured along principal directions. Intrinsic properties\nand structural information were retrieved from the analysis, in excellent\nagreement with information obtained from FESEM images. In the studied samples\nnanoparticles were found to be in close contact to each other within almost\nrandomly oriented clusters. Intercluster mean relative-distance was found to\nvary between 2.2 and 7.5, depending on particles volume fraction.\n

Topic: Characterization and Applications of Magnetic Nanoparticles
Subfield: Biomedical Engineering
Field: Engineering
Domain: Physical Sciences
Distribution Characteristics and Source Analysis of Microplastics in Urban Freshwater Lakes: A Case Study in Songshan Lake of Dongguan, China

Current studies on microplastic pollution mainly focus on marine systems. However, few studies have investigated microplastics in an urban lake. This research intends to use an urban lake (Songshan Lake) as an example to explore the pollution characteristics of microplastics and use the principal component as well as the heat map analysis to discuss the relationships between different shapes of microplastics. According to this study, the average abundance of microplastics in the surface water and surface sediments of Songshan Lake were, respectively, 2.29 ± 0.98 items/m3 and 244 ± 121 items/kg; thin films were the major microplastics in both media; transparent this type of color has the most microplastic content. The particle size of microplastics was mainly 0.18–0.6 mm (43.3%) in surface water and 1–2 mm (48.3%) in surface sediments. The composition included five polymers: polyethylene (PE), polypropylene (PP), polypropylene–polyethylene copolymer (PP–PE copolymer), polystyrene (PS), and polyvinyl chloride (PVC), among which PE (47%) and PP (36%) were the main components. Principal component analysis (PCA) showed that there was a positive correlation among the four shapes of microplastics: films, fragments, foams, and fibers. The heat map analysis showed that the same category of shape distribution features may be similar for each sampling site.

Topic: Microplastics and Plastic Pollution
Subfield: Pollution
Field: Environmental Science
Domain: Physical Sciences