gebhart/patrepeval huggingface dataset:
Cytoskeletal stability and metabolic alterations in primary human macrophages in long-term microgravity (2017)

The immune system is one of the most affected systems of the human body during space flight. The cells of the immune system are exceptionally sensitive to microgravity. Thus, serious concerns arise, whether space flight associated weakening of the immune system ultimately precludes the expansion of human presence beyond the Earth's orbit. For human space flight, it is an urgent need to understand the cellular and molecular mechanisms by which altered gravity influences and changes the functions of immune cells. The CELLBOX-PRIME (= CellBox-Primary Human Macrophages in Microgravity Environment) experiment investigated for the first time microgravity-associated long-term alterations in primary human macrophages, one of the most important effector cells of the immune system. The experiment was conducted in the U.S. National Laboratory on board of the International Space Station ISS using the NanoRacks laboratory and Biorack type I standard CELLBOX EUE type IV containers. Upload and download were performed with the SpaceX CRS-3 and the Dragon spaceship on April 18th, 2014 / May 18th, 2014. Surprisingly, primary human macrophages exhibited neither quantitative nor structural changes of the actin and vimentin cytoskeleton after 11 days in microgravity when compared to 1g controls. Neither CD18 or CD14 surface expression were altered in microgravity, however ICAM-1 expression was reduced. The analysis of 74 metabolites in the cell culture supernatant by GC-TOF-MS, revealed eight metabolites with significantly different quantities when compared to 1g controls. In particular, the significant increase of free fucose in the cell culture supernatant was associated with a significant decrease of cell surface-bound fucose. The reduced ICAM-1 expression and the loss of cell surface-bound fucose may contribute to functional impairments, e.g. the activation of T cells, migration and activation of the innate immune response. We assume that the surprisingly small and non-significant cytoskeletal alterations represent a stable "steady state" after adaptive processes are initiated in the new microgravity environment. Due to the utmost importance of the human macrophage system for the elimination of pathogens and the clearance of apoptotic cells, its apparent robustness to a low gravity environment is crucial for human health and performance during long-term space missions.
Upper Extremity Deep Venous Thrombosis in Cancer Patients with Venous Access Devices - Prophylaxis with a Low Molecular Weight Heparin (Fragmin) (1996)

Central venous access devices are often essential for the administration of chemotherapy to patients with malignancy, but its use has been associated with a number of complications, mainly thrombosis. The true incidence of upper extremity deep vein thrombosis (DVT) in this setting is difficult to estimate since there are very few studies in which DVT diagnosis was based on objective tests, but its sequelae include septic thrombophlebitis, loss of central venous access and pulmonary embolism. We performed an open, prospective study in which all cancer patients who underwent placement of a long-term Port-a-Cath (Pharmacia Deltec Inc) subclavian venous catheter were randomized to receive or not 2500 IU sc of Fragmin once daily 90 days. Venography was routinely performed 90 days after catheter insertion, or sooner if DVT symptoms had appeared. Our aims were: 1) to investigate the effectiveness of low doses of Fragmin in preventing catheter-related DVT; and 2) to try to confirm if patients with high platelet counts are at a higher risk to develop subclavian DVT, as previously suggested. On the recommendation of the Ethics Committee, patient recruitment was terminated earlier than planned: DVT developed in 1/16 patients (6%) taking Fragmin and 8/13 patients (62%) without prophylaxis (Relative Risk 6.75; 95% CI: 1.05-43.58; p = 0.002, Fisher exact test). No bleeding complications had developed. As for prediction of DVT, there was a tendency towards a higher platelet count in those patients who subsequently developed DVT, but differences failed to reach any statistical significance (286 +/- 145 vs 207 +/- 81 x 10(9)/1; p = 0.067). According to our experience, Fragmin at the dosage used proved to be both effective and safe in these patients.
Volatile Aroma Constituents of Three Labiatae Herbs Growing Wild in the Karakoram-Himalaya District and Their Antifungal Activity by Vapor Contact (2001)

Abstract Ethyl acetate extracts from the flowers and leaves of Perovskia ahrotanoides Karel., Nepeta juncea Benth. and Thymus linearis Benth. growing wild at 2000–3500 m a.s.l. in the Karakoram-Himalaya district were analyzed by GC/MS. The majorvolatile constituents were 1,8-cineole (24.4–27.1%) and α-pinene (18.2–23.2%) for P. abrotanoides, and nepetalactone (71.8%) for N.juncea. Two chemotypes of T. linearis were found in different area, a thymol/carvacrol type in the areas of Hunza and Rupal Valley, and a geraniol/geranyl acetate type in the area of Rakaposhi Valley. Herbs and their major constituents of N.juncea and T. linearis showed potent antifungal activity by vapor contact, but those of P. abrotanoides showed no significant activity.
Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides (2021)

Antisense oligonucleotides (ASOs) have the ability of binding to endogenous nucleic acid targets, thereby inhibiting the gene expression. Although ASOs have great potential in the treatment of many diseases, the search for favorable toxicity profiles and distribution has been challenging and consequently impeded the widespread use of ASOs as conventional medicine. One strategy that has been employed to optimize the delivery profile of ASOs, is the functionalization of ASOs with cationic amine groups, either by direct conjugation onto the sugar, nucleobase or internucleotide linkage. The introduction of these positively charged groups has improved properties like nuclease resistance, increased binding to the nucleic acid target and improved cell uptake for oligonucleotides (ONs) and ASOs. The modifications highlighted in this review are some of the most prevalent cationic amine groups which have been attached as single modifications onto ONs/ASOs. The review has been separated into three sections, nucleobase, sugar and backbone modifications, highlighting what impact the cationic amine groups have on the ONs/ASOs physiochemical and biological properties. Finally, a concluding section has been added, summarizing the important knowledge from the three chapters, and examining the future design for ASOs.
P3-06-04: Sno/miRNA Expression Via Next Generation Sequencing: Variation in Patients before and after Treatment. (2011)

Abstract Background Aberrant expression of small RNA molecules has been shown in breast cancer. It is yet unclear if variation exists in small RNA molecule expression in response to treatment. Since next generation sequencing offers more globally sensitive detection of sno and miRNAs, we performed an RNA-seq study to explore patients pre- and post- brief exposure to treatment. Methods: We sequenced transcriptomes of frozen biopsy samples from 8 breast cancer patients enrolled in a clinical trial for neoadjuvant therapy using trastuzumab (HER2 positive) or bevacizumab (HER2 negative) with chemotherapy. Tumor core biopsies were taken before and after 10 days of either biologic or nab-paclitaxel treatment and stored in OCT compound. Total RNA was extracted and libraries were constructed for the 16 samples using TruSeq (Illumina). We performed 74bp paired-end sequencing with the Illumina GAII platform. Sequences were aligned to the sno/miRNA track (containing 928 miRNAs and 413 snoRNAs) in UCSC and read counts were determined using Bowtie. We performed differential miRNA and snoRNA expression analysis pair-wise in all pre- and post-therapy samples. Given that miRNA deregulation relies on their protein-coding gene targets, we analyzed the predicted targets of the significantly varying miRNAs for functional enrichment. Results: Each sample had on average 46 million paired-end reads, of which on average 70% were mapped to the human genome. Overall, we detected 138 miRNAs in at least one sample, with each sample expressing 33 miRNAs on average. We detected a total of 11 miRNAs (7%) that showed significant differential expression with treatment. Interestingly, 6 of these miRNAs varied in all patients. The predicted targets of these miRNAs were enriched in DNA-dependent transcription, gene expression, cell proliferation and cell communication. Similarly, we detected 202 snoRNAs in at least one sample, with each sample expressing 87 snoRNAs on average. Of these, we found 21 snoRNAs (10%) to vary significantly upon treatment and 6 of these snoRNAs showed expression changes in all patients. Conclusions: These results suggest that variation in sno/miRNA expression may play a role in response to treatment. The consistent variation of sno/miRNAs in response to treatment suggests shared small RNA-mediated mechanisms. If validated, these results suggest that next generation sequencing technologies will allow lead to improved methods of stratifying, subclassifying and managing breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-06-04.
Reducing capacity and conflict misses using Set Saturation Levels (2010)

The well-known memory wall problem has motivated wide research in the design of caches. Last-level caches, whose misses can stall the processors for hundreds of cycles, have received particular attention. Strategies to modify adaptably the cache insertion, promotion, eviction and even placement policies have been proposed, some techniques being better at reducing different kinds of misses. For example changes in the placement policy of a cache, which are a natural option to reduce conflict misses, can do little to fight capacity misses, which depend on the relation between the working set of the application and the cache size. Nevertheless, other techniques such as the recently proposed dynamic insertion policy (DIP), whose aim is to retain a fraction of the working set in the cache when it is larger than the cache size, attack primarily capacity misses. In this paper we present a coordinated strategy to reduce both capacity and conflict misses by changing the placement and insertion policies of the cache. Our strategy takes its decisions based on the concept of the Set Saturation Level (SSL), which tries to measure to which degree a set can hold its working set. Despite requiring only less than 1% storage overhead, our proposal, called Bimodal Set Balancing Cache, reduced the average miss rate of a baseline 2MB 8-way second level cache by 16%, which translated into an average IPC improvement of 4.8% in our experiments.
Abstract 3049: Hornerin as a novel therapeutic target for pancreatic cancer (2019)

Abstract Background and aim - Through our functional proteomics screening efforts, we recently identified hornerin (HRNR) as a protein expressed on the cell surface of both cancer and cancer blood vessels. Hornerin is a member of the S100 family of proteins, a group of calcium binding proteins involved in the maintenance of calcium homeostasis, as well other fundamental cellular processes and signaling cascades. Several family members have been implicated in a variety of cancers, with evidence demonstrating that altered expression of S100 proteins was associated with tumor progression and prognosis. Therefore, we hypothesized that HRNR may represent an important therapeutic target for cancer. Method - De-identified human tumor microarray specimens underwent standard immunohistochemistry (IHC) procedure to determine HRNR expression in various type of cancer. Standard westernblot were also used to assess HRNR expression in eleven epithelial PDAC cell lines. Analysis of HRNR expression in cellular compartments was performed after differential centrifugation of PDAC cell lysates. Cell surface HRNR expression was further validated by immunofluorescence on non-permeabilized cells. Additionally, cells from 4 different renal carcinoma (RCC) PDX models were infected with human HRNR shRNA lentiviral particles in order to silence HRNR expression. Those cells were then injected subcutaneously into immunocompromised nude mice and assessed for tumor growth. Molecular mechanism of HRNR was evaluated via western blot. Effect of blocking HRNR on cancer in vitro and in vivo using a HRNR specific antibody was determined. Results - Based on IHC scoring, HRNR expression has been observed in twenty-one different types of cancer among which are PDAC and renal cancer. Expression of HRNR in tumor cells and on the cell surface of cancer was confirmed through cell fractionation and immunofluorescence. Validation of HRNR as an important cancer therapeutic target was demonstrated through siRNA knockout studies. PDX models of renal cancer that were devoid of HRNR expression were unable to form tumors in vivo. As members of the S100 family have been shown to activate signaling pathways important for proliferation and migration, we hypothesized that HRNR would be able to activate proteins in these signaling cascades. Western blot analysis of cells treated with recombinant HRNR revealed the activation of AKT and ERK and the stabilization of EGFR. Therefore, we evaluated the efficacy of a HRNR targeted antibody as a therapeutic. Treatment with the HRNR targeted antibody resulted in a decrease in cell proliferation and complete cell death that was HRNR specific. Conclusion - HRNR plays an important role in cancer and represents a novel therapeutic target. Citation Format: Julien Dimastromatteo, Kimberly A. Kelly. Hornerin as a novel therapeutic target for pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3049.
ChemInform Abstract: Reductive Cleavage of the O‐C(8) Bond in 5′‐O,8‐Cycloadenosines. Intramolecular Protection of the 8‐Position and the 5′‐Hydroxy Group in Adenosines. (1988)

Abstract Selective cleavage of the N6‐acyl‐5'‐O,8‐cycloadenosines (I) is achieved by treatment with sodium cyanoborohydride, yielding the N6‐acyladenosines (II).
High-Voltage Electrolytes Based on Adiponitrile for Li-Ion Batteries (2008)

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Electromagnetic induction in a spherical earth with non-uniform oceans and continents in electric contact with the underlying medium-I. Theory, method and example (1990)

This paper presents basic principles of the iterative-dissipative method and main points of its numerical realization. A spherical earth model consisting of a thin non-uniform surface layer being in galvanic contact with an underlying stratified medium is considered. The current system induced by a uniform magnetic field in the model with a realistic distribution of surface conductance is calculated. It is shown that leakage currents are significant even for the earth model with a highly resistive crust and upper mantle.
Demonstration and Validation of a Replacement Alternative to the Chromate Wash Primer DOD-P-15328D (2006)

Abstract : The purpose of the DOD-P-15328D wash primer is to enhance corrosion resistance through the passivation of the metal surface. In the U.S. Army Chemical Agent Resistant Coating (CARC) System, the metal surface is coated with a wash primer, overcoated with an epoxy primer, and followed by a camouflage urethane topcoat. Several coating procedures specify the use of the wash primer, DOD-P-15328D, as a surface treatment prior to the application of an epoxy primer/polyurethane topcoat CARC system. The current wash primer is a low-solids, solvent-based polyvinyl butyral that contains phosphoric acid and zinc chromate that promotes adhesion and minimizes corrosion. This coating contains large amounts of volatile organic compounds (VOCs) and hazardous air pollutants (HAPs) that impact coating operations due to air pollution regulations that may require the use of control devices to reduce the total VOC/HAP emissions to the atmosphere. The U.S. Army Research Laboratory has evaluated new, water-reducible wash primers that do not contain hexavalent chromium and significantly minimize VOC and HAP potential emissions during coating operations. Coatings have been extensively tested for accelerated corrosion and adhesion and have successfully completed 3 years of outdoor exposure testing. Tests are now required on military equipment to validate the lab and controlled testing previously completed. The ultimate objective of the process is to demonstrate that the low VOC wash primers can provide a drop-in solution to the environmental issues associated with the solvent-based primer currently in use, providing equal or better performance, involving no significant changes to the application and stripping procedures currently being used. The field demonstration of this coating was conducted at Letterkenny Army Depot facility and prepared on an Engagement Control Station Patriot truck unit.
Non‐invasive algorithms for liver fibrosis (2011)

We are impressed by the interesting article by Sebastiani et al.1 The authors are congratulated for conducting a multicentre, large-scale validation study of three algorithms to predict liver fibrosis in chronic hepatitis C patients. We would like to address a few issues. The three algorithms under investigation, sequential algorithm for fibrosis evaluation (SAFE biopsy), Fibropaca algorithm and Leroy algorithm, are based on either sequential or synchronous combination of FibroTest, Forns’ index and aspartate aminotransferase-to-platelet ratio index. Such complicated algorithms may be difficult to apply in the busy clinic setting. In contrast, physical measurements such as transient elastography are more user-friendly.2–4 In a multicentre prospective study, transient elastography was superior to several biomarkers of liver fibrosis in predicting liver cirrhosis.5 One limitation of transient elastography is the increase in liver stiffness measurement with higher ALT levels independent of fibrosis staging.3, 6 Owing to the different mechanisms of serum formulae and transient elastography, there is increasing enthusiasm to combine these two modalities to increase the accuracy. For example, the addition of Forns’ index increased the accuracy of transient elastography in chronic hepatitis B patients.7 Another limitation of transient elastography is the lower success rate in obese patients,8, 9 whereas serum markers can be performed essentially in all patients. On the other hand, decrease in absolute liver stiffness value was found to be unreliable to indicate regression of liver fibrosis,10 whereas serum markers have not been well-studied as an on-treatment monitoring of liver fibrosis. We believe that transient elastography and serum markers do have a supplementary role to each other. Finally, we must not forget that the reference standard, liver biopsy, is imperfect. Fibrosis is also a surrogate marker and not the final target. More studies are needed to validate the non-invasive tests in predicting important clinical outcomes. Declaration of personal interests: Vincent Wong has served in the advisory boards of Novartis, Roche, Gilead and Otsuka. He is also a speaker for Abbott Diagnostics, Novartis, Roche, Bristol-Myers Squibb and Echosens. Grace Wong has served as a speaker for Echosens. Declaration of funding interests: None.
Optimisation du profil de dopage d'un MESFET réalisé par implantation ionique (1986)

On analyse l'interdépendance entre les performances d'un transistor à effet de champ en arséniure de gallium et son profil de dopage réalisé par implantation ionique. On étudie en particulier l'influence des conditions d'implantation (énergie et dose implantées) ainsi que celle du creusement de grille (« recess ») préalablement à la réalisation de la barrière Schottky. Les résùltats théoriques ont été obtenus à l'aide d'un simulateur permettant d'accéder aux propriétés statiques et dynamiques petits signaux du transistor à effet de champ pour tout profil de dopage non uniforme. Le temps de calcul a été réduit au maximum en associant des techniques analytiques et numériques. Le fonctionnement général du logiciel ainsi que les principes du calcul de toutes les caractéristiques électriques du composant sont détaillés. Les résultats de la simulation sont comparés aux résultats expérimentaux obtenus sur des structures réalisées en faisant varier les conditions d'implantation et la profondeur du creusement de grille. Enfin, l'influence du profil de dopage sur chacun des éléments du schéma équivalent du transistor à effet de champ GaAs est discutée en vue d'une optimisation des performances micro-ondes.
Prognostic significance of heterologous component in carcinosarcoma of the gynecologic organs: a systematic review and meta-analysis (2023)

PROSPERO Identifier: CRD42022298871.
Do only circulating pyrogenic cytokines act as mediators in the febrile response? A hypothesis (1999)

The classical model of the pathogenesis of fever suggests that pyrogenic cytokines, produced by leucocytes in the bloodstream in response to exogenous pyrogens, represent the distal mediators of the febrile response. They are recognized at the level of the organum vasculosum of the lamina terminalis in the central nervous system, where they induce synthesis of prostaglandins representing the central mediators of the coordinated responses leading to fever. This classical model is challenged by studies showing inconsistencies between the febrile response and the cytokine pattern, as well as by data demonstrating paradoxical hyperfebrile reactions in knock-out mice lacking cytokines or cytokine receptors. Moreover, no measurable cytokine concentrations are to be found in a variety of specific patients groups with febrile conditions. There are recent data in the literature suggesting that alternative pathways may be involved in the induction of fever, ranging from the use of vagal fibres to transmit the signals leading to fever, to local production of cytokines at the level of the hypothalamus, or the use of membrane-bound cytokines as mediators. A multipathway mechanism for the induction of fever is suggested.