gebhart/patrepeval huggingface dataset:
Non-invasive Imaging of Idiopathic Pulmonary Fibrosis Using Cathepsin Protease Probes (2016)

Idiopathic pulmonary fibrosis (IPF) is a lethal, chronic, progressive disease characterized by formation of scar tissue within the lungs. Because it is a disease of unknown etiology, it is difficult to diagnose, to predict disease course and to devise treatment strategies. Recent evidence suggests that activated macrophages play key roles in the pathology of IPF. Therefore, imaging probes that specifically recognize these pools of activated immune cells could provide valuable information about how these cells contribute to the pathobiology of the disease. Here we demonstrate that cysteine cathepsin-targeted imaging probes can be used to monitor the contribution of macrophages to fibrotic disease progression in the bleomycin-induced murine model of pulmonary fibrosis. Furthermore, we show that the probes highlight regions of macrophage involvement in fibrosis in human biopsy tissues from IPF patients. Finally, we present first-in-human results demonstrating non-invasive imaging of active cathepsins in fibrotic lesions of patients with IPF. Together, our findings validate small molecule cysteine cathepsin probes for clinical PET imaging and suggest that they have the potential to be used to generate mechanistically-informative molecular information regarding cellular drivers of IPF disease severity and progression.
Multi-Level Proactive Security Auditing for Clouds (2019)

Runtime cloud security auditing plays a vital role in mitigating security concerns in a cloud. However, there currently does not exist a comprehensive solution that can protect a cloud tenant against the threats rendered from the multiple levels (e.g., user, virtual, and physical) of the cloud design. Furthermore, most of the existing solutions suffer from slow response time and require significant manual efforts. Therefore, a simple integration of the existing solutions for different levels is not a practical solution. In this paper, we propose a multilevel proactive security auditing system, which overcomes all the above-mentioned limitations. To this end, our main idea is to automatically build a predictive model based on the dependency relationships between cloud events, proactively verify the security policies related to different levels of a cloud by leveraging this model, and finally enforce those policies on the cloud based on the verification results. Our experiments using both synthetic and real data show the practicality and effectiveness of this solution (e.g., responding in a few milliseconds to verify each level of the cloud).
Ein daten- und modellgesteuerter Ansatz zur Behandlung maligner Tumoren (2019)

Alle Menschen sind einzigartig und so sind es auch ihre Krankheiten. Genome, Erkrankungsverläufe, Verhalten und Lebensstile sind unterschiedlich; es ist daher nicht erstaunlich, dass Menschen auch auf dieselben Medikamente unterschiedlich reagieren. Gerade Krebserkrankungen sind komplex und heterogen: Sie entstehen in Patienten mit individuellen Genomen und in Zellen mit je eigenen Epigenomen, sie entwickeln und entfalten sich auf der Basis zufälliger Prozesse. Dabei hängt das Ansprechen auf eine Therapie nicht nur von der einzelnen Tumorzelle, sondern auch von vielen patienteneigenen Faktoren ab. Die Entscheidung für eine optimale Behandlung erfordert daher eine tiefgehende molekulare Analyse, die sowohl den Patienten als auch den Tumor einschließt (z. B. „comprehensive molecular tumor analysis“ [CMTA]) und anhand derer sich das Ansprechen auf mögliche personalisierte Therapien deutlich besser vorhersagen lässt. Zurzeit befinden wir uns an einem Wendepunkt: Technologische Fortschritte, verringerte Kosten für Sequenzierung und andere molekulare Analysen sowie Weiterentwicklungen in der Datenverarbeitung können jetzt zusammengeführt werden und werden zum Fundament für den Aufbau eines datengesteuerten Ansatzes in der personalisierten Onkologie. Der Beitrag diskutiert die umfassende molekulare Charakterisierung einzelner Tumoren und Patienten als Basis nicht nur für die aktuelle Präzisionsonkologie, sondern auch für Rechenmodelle („digitale Zwillinge“), welche die Grundlage einer künftig tatsächlich personalisierten Therapieauswahl bilden werden.
Right dorsal colitis in the horse: minireview and reports on three cases in Ireland (2004)

: Right dorsal colitis (RDC) is an ulcerative inflammatory bowel disorder of the horse that has been associated with the administration of non-steroidal anti-inflammatory drugs (NSAIDs), particularly in horses treated when dehydrated or toxaemic. The acute form of RDC may result in profuse diarrhoea, severe colic, dehydration, endotoxic shock and even death; the chronic form may be manifest by mild to moderate intermittent colic, ventral oedema and weight loss with or without diarrhoea. The most consistent laboratory findings are anaemia, hypoproteinaemia, hypoalbuminaemia and hypocalcaemia. Medical management of RDC requires avoidance of NSAIDs, of stressful experiences and of large-volume diets. Specific medications such as sucralfate and metronidazole have been used to treat RDC in the horse. The use of dietary additions such as psyllium and corn oil has been mentioned in the literature.RDC has not been reported previously in Ireland or Britain; here we report that the condition was diagnosed in three horses in Ireland on the bases of a history of phenylbutazone therapy, clinical signs, clinical pathology and ultrasonography. In two of the three horses the diagnosis was confirmed by direct inspection of the affected colon at celiotomy.
Influence of Solution Composition and Temperature on the Crystal Form of Sodium Dehydroacetate (2017)

Abstract The slurry transformation of sodium dehydroacetate monohydrate with different compositions of water and methanol was investigated. The water content and temperature did not only affect the solubility but also the crystal form of the precipitated material. A new needle hydrate form of sodium dehydroacetate appeared on the surface of the anhydrate when the water content was between 2 % and the critical transformation values which varied with temperature. The results revealed that the needle hydrate was a new form of sodium dehydroacetate monohydrate. A possible explanation for these observations was found in the relationship between the change of water content, the interaction between solute and solvent, and the influence of supersaturation.
Prospección de nuevos antiinfecciosos, desde la naturaleza a la síntesis química (2020)

La aparicion de resistencias en los micoorganismos a los antiifecciosos utilizados durante las ultimas decadas, ha provocado la necesidad de desarrollar nuevos farmacos con el fin de hacerles frente. Los productos naturales, que sirvieron como base para el tratamiento de enfermedades y cuya investigacion por parte de las industrias farmaceuticas durante los anos 90 sufrio un importante descenso, vuelven a protagonizar un repunte en la busqueda de nuevos candidatos y cabeza de serie de origen natural debido a la especificidad que poseen sobre las dianas biologicas.
La tesis que se presenta, engloba un conjunto de proyectos con el objetivo de encontrar nuevos candidatos a traves de distintas estrategias en la busqueda de otros farmacos desde la naturaleza a la optimizacion de un candidato por sintesis quimica.
En el primer capitulo se ha aislado un alcaloide con esqueleto terpenico en el cual se ha elucidado su estructura: con tecnicas de espectroscopia de RMN, espectrometria de masas junto con el estudio de su susceptibilidad biologica, antibiotica y antifungica.
En el segundo capitulo se ha optimizado por sintesis quimica un cabeza de serie denominado fenildihidrazina con actividad antifungica por estudios de estructuras actividad junto con estudios de toxicidad bastante prometedores.
En el tercer capitulo se ha puesto a punto la sintesis de derivados del acido muramico y con ellos se han sintetizado unas serie de cores para finalmente unirlos y formar distintos glicomimeticos a traves de reacciones de click chemistry.
Oncogenic Mutant p53 Gain of Function Nourishes the Vicious Cycle of Tumor Development and Cancer Stem-Cell Formation (2016)

More than half of human tumors harbor an inactivated p53 tumor-suppressor gene. It is well accepted that mutant p53 shows an oncogenic gain-of-function (GOF) activity that facilitates the transformed phenotype of cancer cells. In addition, a growing body of evidence supports the notion that cancer stem cells comprise a seminal constituent in the initiation and progression of cancer development. Here, we elaborate on the mutant p53 oncogenic GOF leading toward the acquisition of a transformed phenotype, as well as placing mutant p53 as a major component in the establishment of cancer stem cell entity. Therefore, therapy targeted toward cancer stem cells harboring mutant p53 is expected to pave the way to eradicate tumor growth and recurrence.
τ Protein and the Neurofibrillary Pathology of Alzheimer’s Disease (1997)

Alzheimer’s disease is characterized clinically by a progressive loss of memory and other cognitive functions, resulting in a profound dementia. The intellectual decline is accompanied by the progressive accumulation in the brain of insoluble fibrous material, extracellularly in the form of senile plaques, and intracellularly in the form of neurofibrillary lesions. Alzheimer’s disease is genetically heterogenous, with different primary causes leading to the same phenotype and neuropathology. It is therefore possible that the activation of several distinct pathological pathways can lead to the disease, with neuritic plaques and neurofibrillary lesions representing the points of convergence of these events. It follows that a study of the mechanisms that lead to the formation of plaques and neurofibrillary lesions is essential for an understanding of the pathogenesis of all forms of Alzheimer’s disease. The formation of neurofibrillary lesions is believed to lead to the symptoms of the disease, which result most probably from the degeneration of nerve cells in cerebral cortex and hippocampal formation, with ensuing neuronal cell loss and reduction in synapse numbers.
The Proprotein Convertase PC7 (2010)

The zymogen activation mechanism and physiological functions of the most ancient and highly conserved basic amino acid-specific proprotein convertase 7 (PC7) are not known. Herein, we characterized the biosynthesis, subcellular localization, and trafficking of the membrane-bound full-length rat and human PC7. The prosegment of PC7 is primarily secreted alone as a non-inhibitory protein via the conventional, Golgi-dependent, secretory pathway. Mature PC7 is partially sulfated and thus reaches the cell surface via the conventional route. However, a fraction of PC7 reaches the cell surface through a brefeldin A- and COPII-independent unconventional secretory pathway. The latter trafficking may explain the rapid (<10 min) transit of a fraction of PC7 from the ER to the cell surface. Electron microscopy further confirmed the localization of PC7 to the cell surface of HEK293 cells. Within the cytosolic tail, only two cysteines (Cys(699) and Cys(704)) are palmitoylated, but this modification does not affect the choice of trafficking pathway. Swapping the transmembrane-cytosolic tail (TMCT) sequences of the convertases Furin and PC7 revealed that PC7(TMCT-Furin) is much more sulfated and hence traffics more efficiently through the conventional secretory pathway. In contrast, the Furin(TMCT-PC7) is no longer sulfated and thus reaches the cell surface by the unconventional pathway. Because trafficking of PC7(CT-Furin) and Furin(CT-PC7) resemble their wild type counterparts, we deduce that the transmembrane domain of PC7 regulates the sorting of PC7 toward the unconventional secretory pathway. In conclusion, PC7 is distinct from other proprotein convertases in its zymogen activation, subcellular localization, and trafficking.
Observation of a Thermally Induced Bora‐Nazarov Cyclization at a Phosphole Framework (2015)

The reaction of the bis(enynyl)phosphanes 6 a,b with the electrophilic borane reagents RB(C6 F5 )2 (R=C6 F5 , CH2 CH2 Ph, CH3 ) gave phospholes cleanly in a 1,1-carboboration reaction sequence. Depending on the steric bulk, the resulting 2,5-alkenylphospholes underwent a thermally induced bora-Nazarov type cyclization. The equilibrium situation of these examples of a bora-Nazarov type cyclization was investigated in detail by NMR spectroscopy, X-ray crystal structure analysis, and DFT calculations.
Longueur de cohérence d'un condensat de Bose Einstein dans un piège très anisotrope (2004)

Nous mesurons la longueur de coherence axiale d'un condensat de Bose Einstein ayant un rapport d'aspect entre 60 et 100. Nous utilisons pour cela un interferometre atomique qui permet d'obtenir directement la fonction de correlation du condensat. Les premieres courbes obtenues montrent une dependance de la longueur de coherence avec la temperature et temoignent de la presence de quasicondensats.
Nitric oxide synthase in the enteric nervous system of the rainbow trout, Salmo gairdneri . (1993)

The distribution of nitric oxide synthase (NOS) was determined in the gastrointestinal tract of the rainbow trout, Salmo gairdneri. NOS immunoreactivity and the NADPH diaphorase histochemical reaction were co-localized in nerve cells in the myenteric ganglia. However, only about 60% of NADPH diaphorase-stained nerve cells in the vagus nerve trunks were immunoreactive for NOS. Reactive myenteric nerve cells were found throughout the gastrointestinal tract, comprising about 10-15% of all nerve cells. Reactive nerve cells and fibres appeared in the myenteric ganglia and nerve trunks. The circular muscle was innervated by reactive nerve fibres throughout the gastrointestinal tract. Some NOS-containing cell bodies were also in this layer. The submucous plexus contained reactive nerve fibres in each region of the gut; in the large intestine a few reactive nerve cell bodies were also seen in this plexus. The muscle in the mucosal folds of the large intestine was densely innervated. The observations suggest that nitric oxide is an enteric transmitter in teleost fish, as it is in mammals.
Probing a Potassium Channel Pore with an Engineered Protonatable Site (1995)

Blockade by intracellular cations reduces outward conduction of K+ in inward rectifier K+ channels. Mutations of residue 171 in the second transmembrane (M2) segment of the ROMK1 channel have been found to affect the affinity for blockade by intracellular Mg2+ and polyamines. In the present study, we examined the mechanism by which this residue mediates blockade by placing a proton acceptor (histidine) at this position. The results allow us to draw two conclusions. First, the side chain of residue 171 is located in the ion conduction pore about halfway across the transmembrane voltage drop. Second, its side chain comes into close contact and interacts electrostatically with a blocking ion.
State of the art spatial visualization of the response of neovascularisation to anti-vascular endothelial growth factor therapy (2022)

The ability to directly observe the effect of <i>anti</i>-VEGF injections on a RNV using three-dimensional OCTA was successfully demonstrated. This can be useful in patients with previous allergic and potentially lethal complications to fluorescein. In addition, enhanced three-dimensional spatial display of RNV leads to a greater understanding of the perfusion profile and the anatomical changes that occur in ocular neovascularization relative to surrounding tissue. This has the potential to provide insight into the pathobiology of angiogenesis.
Vocal-Accompaniment Compatibility Estimation Using Self-Supervised and Joint-Embedding Techniques (2021)

We propose a learning-based method of estimating the compatibility between vocal and accompaniment audio tracks, <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">i.e.</i> , how well they go with each other when played simultaneously. This task is challenging because it is difficult to formulate hand-crafted rules or construct a large labeled dataset to perform supervised learning. Our method uses self-supervised and joint-embedding techniques for estimating vocal-accompaniment compatibility. We train vocal and accompaniment encoders to learn a joint-embedding space of vocal and accompaniment tracks, where the embedded feature vectors of a compatible pair of vocal and accompaniment tracks lie close to each other and those of an incompatible pair lie far from each other. To address the lack of large labeled datasets consisting of compatible and incompatible pairs of vocal and accompaniment tracks, we propose generating such a dataset from songs using singing voice separation techniques, with which songs are separated into pairs of vocal and accompaniment tracks, and then original pairs are assumed to be compatible, and other random pairs are not. We achieved this training by constructing a large dataset containing 910,803 songs and evaluated the effectiveness of our method using ranking-based evaluation methods.
Multi-Frame Cross-Entropy Training for Convolutional Neural Networks in Speech Recognition (2019)

We introduce Multi-Frame Cross-Entropy training (MFCE) for convolutional neural network acoustic models. Recognizing that similar to RNNs, CNNs are in nature sequence models that take variable length inputs, we propose to take as input to the CNN a part of an utterance long enough that multiple labels are predicted at once, therefore getting cross-entropy loss signal from multiple adjacent frames. This increases the amount of label information drastically for small marginal computational cost. We show large WER improvements on hub5 and rt02 after training on the 2000-hour Switchboard benchmark.
Higgs boson production cross-section measurements and their EFT interpretation in the $$4\ell $$ decay channel at $$\sqrt{s}=$$13 TeV with the ATLAS detector (2020)

Abstract Higgs boson properties are studied in the four-lepton decay channel (where lepton = e , $$\mu $$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mi>μ</mml:mi> </mml:math> ) using 139 $$\hbox {fb}^{-1}$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:msup> <mml:mtext>fb</mml:mtext> <mml:mrow> <mml:mo>-</mml:mo> <mml:mn>1</mml:mn> </mml:mrow> </mml:msup> </mml:math> of proton–proton collision data recorded at $$\sqrt{s}=$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:msqrt> <mml:mi>s</mml:mi> </mml:msqrt> <mml:mo>=</mml:mo> </mml:mrow> </mml:math> 13 TeV by the ATLAS experiment at the Large Hadron Collider. The inclusive cross-section times branching ratio for $$H\rightarrow ZZ^*$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mi>H</mml:mi> <mml:mo>→</mml:mo> <mml:mi>Z</mml:mi> <mml:msup> <mml:mi>Z</mml:mi> <mml:mo>∗</mml:mo> </mml:msup> </mml:mrow> </mml:math> decay is measured to be $$1.34 \pm 0.12$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mn>1.34</mml:mn> <mml:mo>±</mml:mo> <mml:mn>0.12</mml:mn> </mml:mrow> </mml:math> pb for a Higgs boson with absolute rapidity below 2.5, in good agreement with the Standard Model prediction of $$1.33 \pm 0.08$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mn>1.33</mml:mn> <mml:mo>±</mml:mo> <mml:mn>0.08</mml:mn> </mml:mrow> </mml:math> pb. Cross-sections times branching ratio are measured for the main Higgs boson production modes in several exclusive phase-space regions. The measurements are interpreted in terms of coupling modifiers and of the tensor structure of Higgs boson interactions using an effective field theory approach. Exclusion limits are set on the CP-even and CP-odd ‘beyond the Standard Model’ couplings of the Higgs boson to vector bosons, gluons and top quarks.
Does nitric oxide mediate the increases in cerebral blood flow elicited by hypercapnia? (1992)

The endothelium-derived relaxing factor (EDRF), probably nitric oxide (NO) or a closely related compound (EDRF/NO), is a potent vasodilator that appears to regulate vascular tone in several vascular beds. I have investigated whether EDRF/NO is also involved in the regulation of the cerebral circulation--in particular, whether EDRF/NO participates in the increases in cerebral blood flow elicited by hypercapnia. Rats were anesthetized with halothane, 1-2% (vol/vol), paralyzed, and artificially ventilated. Arterial pressure was monitored and blood gases were controlled. Cerebral blood flow was continuously monitored through a cranial window over the sensory cortex by a laser-Doppler probe. The window was superfused with Ringer's solution (pH 7.3-7.4 at 37 degrees C). During superfusion with Ringer's solution, hypercapnia (PCO2 = 55.8 +/- 0.8 mmHg) increased cerebral blood flow by 121 +/- 6% (n = 27; P less than 0.001; analysis of variance). Topical superfusion with the NO synthase inhibitors N omega-nitro-L-arginine (1 mM) attenuated the cerebrovasodilation by 93 +/- 6% (n = 8). In contrast, the vasodilation elicited by topical papaverine (1 mM) was not affected by N omega-nitro-L-arginine (n = 10). Application of N omega-nitro-D-arginine (1 mM) did not affect the cerebrovasodilation elicited by hypercapnia (P greater than 0.05; n = 8). N omega-Methyl-L-arginine (1 mM) attenuated the cerebrovasodilation elicited by hypercapnia by 44 +/- 4% (n = 8; P less than 0.001), an effect completely reversed by coapplication of L-arginine (10 mM; P greater than 0.05; n = 13). These findings indicate that the powerful effects of CO2 on the cerebral circulation are mediated by arginine-derived EDRF/NO. EDRF/NO is an important molecular signal whose actions may also include the regulation cerebral circulation.
A Telemedicine Survey among Milan Doctors (2005)

We surveyed physicians' attitudes to the use of telemedicine. A questionnaire was sent to 2987 Italian physicians and 361 responded (12%). The topics covered by the survey were: current telemedicine technology knowledge/usage level; general attitude towards telemedicine applications; perceived efficacy of telemedicine in enhancing quality of care; and intention to use telemedicine. In all, 83% of respondents had heard about telemedicine. Some doctors considered telemedicine to be of limited interest and many physicians were not convinced that it could improve clinical practice. These beliefs were more common among doctors of higher seniority, probably because they are more reluctant to accept change. To reduce such negative evaluations, better dissemination of information about the state of the art of research and development in telemedicine is needed. A logistic regression model was used to determine which factors influenced the intention to use telemedicine. The final model predicted 80% of the responses correctly.
Abstract 154: Inhibition of pancreatic cancer Panc-1 cell migration by omeprazole is dependent on aryl hydrocarbon receptor activation of JNK (2019)

Abstract Aryl hydrocarbon receptor (AhR)-active pharmaceuticals were screened as inhibitors of pancreatic cancer cell invasion and identified two compounds, omeprazole, that inhibited invasion. Inhibition of highly invasive Panc1 cell invasion by omeprazole involves an AhR-dependent non-genomic pathway, and omeprazolemediated inhibition of Panc1 cell invasion was dependent on Jun-N-terminal kinase and mitogen-activated kinase kinase 7 (MKK7). Results of RNAseq studies indicate that omeprazole induced an AhR-dependent downregulation of several pro-invasion factors including activated leukocyte cell adhesion molecule, long chain fatty acid CoA-synthase, stathmin 3 and neuropillin 2, and the specific functions of these genes are currently being investigated. Citation Format: Unho Jin, Keshav Karki, Stephen Safe. Inhibition of pancreatic cancer Panc-1 cell migration by omeprazole is dependent on aryl hydrocarbon receptor activation of JNK [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 154.