gebhart/patrepeval huggingface dataset:
Vascular Function Measured by Fingertip Thermal Reactivity Is Impaired in Patients With Metabolic Syndrome and Diabetes Mellitus (2009)

Digital thermal monitoring (DTM) of vascular function has already been shown to correlate well with coronary artery calcium (CAC) score and coronary artery disease. To determine its utility in the metabolic syndrome (MS) and diabetes mellitus (DM), 233 asymptomatic patients with DM/MS but without coronary artery disease underwent DTM during and after 5 minutes of supra-systolic arm cuff inflation, as well as CAC. Post-cuff deflation adjusted temperature rebound (aTR) was lower in MS and DM compared with the normal group. The odds ratio of lowest vs upper 2 tertiles of aTR was 2.3 for MS and 3.5 for DM compared with the normal group, independent of age, sex, and risk factors. The area under the receiver operating characteristic curve to predict CAC > or =100 was 0.69 for metabolic status (DM/MS), 0.79 for aTR, and 0.87 for both. This study demonstrates that vascular dysfunction measured by DTM is associated with DM/MS and could potentially be used to detect asymptomatic individuals with increased subclinical atherosclerosis.
Application of stable isotopic tracing in an ex-vivo system to reveal heterogeneous patterns of androgen metabolism in localized, hormone-naïve prostate cancer. (2017)

109 Background: The 5α-androstanedione (5α-dione) pathway is the demonstrated route through which adrenal precursor steroids bypass testosterone (T) to form dihydrotestosterone (DHT) in metastatic castration-resistant prostate cancer (mCRPC). However, accessible pathways of DHT synthesis are less clear in localized, hormone-naïve prostate cancer (HNPCa), where steroidogenic enzyme expression may differ and circulating T and adrenal steroids could act as competing substrates for 5α-reductase. We employed a dual substrate, ex-vivo system with selective stable isotopic labeling of DHT precursors to better understand alterations in androgen synthesis that occur in the transition of HNPCa to mCRPC. Methods: Under IRB approval and patient consent, tumor and adjacent benign prostate tissues were procured from radical prostatectomy specimens of men with HNPCa (n = 16). Tissues were grossly homogenized and incubated ex-vivo in serum-free media spiked with 1 µM of 13 C 3 -AD +/- equimolar unlabeled T. Media was collected over 48 hours and subjected to liquid-liquid extraction to capture free and glucuronidated steroid metabolites for analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Both AD and T were readily 5α-reduced in treated prostate tissues. 13 C labeling revealed DHT originating from metabolism of AD. Co-incubation with T did not dramatically alter the efficiency of AD metabolism. Minimal differences were found in metabolism between PZ and TZ tissue. No glucuronidated steroid was detected in media, in contrast to in prostate cancer cell lines and xenograft tumor tissue. Considerable heterogeneity was observed in measurements of reaction efficiency across different patients. Conclusions: AD is an active substrate for 5α-reductase comparable to T in HNPCa. Adrenal steroids may therefore contribute to DHT in HNPCa via the 5α-dione pathway. Metabolic heterogeneity may reflect currently unappreciated genotypic differences in patient tumors.
Designing dependable storage solutions for shared application environments (2006)

The costs of data loss and unavailability can be large, so businesses use many data protection techniques, such as remote mirroring, snapshots and backups, to guard against failures. Choosing an appropriate combination of techniques is difficult because there are numerous approaches for protecting data and allocating resources. Storage system designers typically use ad hoc techniques, often resulting in over-engineered, expensive solutions or under-provisioned, inadequate ones. In contrast, this paper presents a principled, automated approach for designing dependable storage solutions for multiple applications in shared environments. Our contributions include search heuristics for intelligently exploring the large design space and modeling techniques for capturing interactions between applications during recovery. Using realistic storage system requirements, we show that our design tool can produce designs that cost up to 3X less in initial outlays and expected data penalties than the designs produced by an emulated human design process
Serving Multiple Needs with Rural Landscapes and Agricultural Systems (2004)

One important contribution of agroecology is to provide a framework and an opportunity to focus on systems at the landscape level. The importance of recognizing multifunctional processes and products of rural landscapes has grown in recent years. This is due in part to greater attention to systems dimensions of agriculture and food production, including emergent properties at scales larger than fields or farms. In this chapter, the authors study the mechanisms and implications of how agroecosystems are structured and their major processes or functions in order to better understand how alternative agricultural and food systems work, and to use this information to better design systems for the future. They explore structure and function at the landscape level. The authors then define the importance of mechanisms from lower levels and context and regulation forces provided by higher levels within a spatial hierarchy. They conclude with suggestions about the importance of designing sustainable landscapes.
Optical Interconnect Solution With Plasmonic Modulator and Ge Photodetector Array (2017)

We report on an optical chip-to-chip interconnect solution, thereby demonstrating plasmonics as a solution for ultra-dense, high-speed short-reach communications. The interconnect comprises a densely integrated plasmonic Mach-Zehnder modulator array that is packaged with standard driving electronics. On the receiver side, a germanium photodetector array is integrated with trans-impedance amplifiers. A multicore fiber provides a compact optical interface to the array. We demonstrate 4 × 20 Gb/s on-off keying signaling with direct detection.
On the Structure and Dynamics of Duplex GNA (2011)

Glycol nucleic acid (GNA), with a nucleotide backbone comprising of just three carbons and the stereocenter derived from propylene glycol (1,2-propanediol), is a structural analog of nucleic acids with intriguing biophysical properties, such as formation of highly stable antiparallel duplexes with high Watson-Crick base pairing fidelity. Previous crystallographic studies of double stranded GNA (dsGNA) indicated two forms of backbone conformations, an elongated M-type (containing metallo-base pairs) and the condensed N-type (containing brominated base pairs). A herein presented new crystal structure of a GNA duplex at 1.8 Å resolution from self-complementary 3'-CTC(Br)UAGAG-2' GNA oligonucleotides reveals an N-type conformation with alternating gauche-anti torsions along its (O3'-C3'-C2'-O2') backbone. To elucidate the conformational state of dsGNA in solution, molecular dynamic simulations over a period of 20 ns were performed with the now available repertoire of structural information. Interestingly, dsGNA adopts conformational states in solution intermediate between experimentally observed backbone conformations: simulated dsGNA shows the all-gauche conformation characteristic of M-type GNA with the higher helical twist common to N-type GNA structures. The so far counterintuitive, smaller loss of entropy upon duplex formation as compared to DNA can be traced back to the conformational flexibility inherent to dsGNA but missing in dsDNA. Besides extensive interstrand base stacking and conformational preorganization of single strands, this flexibility contributes to the extraordinary thermal stability of GNA.
Software defined elastic optical networks using OpenFlow (Invited) (2013)

The elastic optical network (EON) is an emergent technology allowing an efficient use of the optical spectrum. In an EON, optical spectrum ranges are adaptively allocated to an optical path according to the IP traffic demand, modulation format and path attributes. The key component of an EON is the dynamic control plane required for reaching full potential with respect to intelligent end‐to‐end optical path provisioning and IP traffic offloading. To this end, many studies have proposed GMPLS‐based control planes for an EON. Despite GMPLS' maturity, it may not be an ideal solution for the deployment in a real operational scenario due to its distributed nature and high complexity, especially for a unified control functionality in IP and EON multi‐layer networks. Alternatively, a software‐define networking approach enabled by OpenFlow, can provide the satisfactory flexibility and centralized intelligence for operators to control an EON, and can arguably match carriers’ requirements in terms of simplicity and manageability. In light of this, in this talk, we present an OpenFlow‐based unified control approach for dynamic optical path provisioning and IP traffic offloading in EONs. We detail the network architecture and required protocol extensions to OpenFlow while highlighting our experimental results on a real EON testbed.
Antirheumatic therapy is associated with reduced complement activation in rheumatoid arthritis (2022)

Patients with active RA had elevated TCC, indicating increased complement activation. TCC decreased with antirheumatic treatment already after 6 weeks. However, only treatment with TNFi±MTX led to sustained reduction in TCC during the 6-month follow-up period. RA patients with endothelial dysfunction had higher baseline TCC compared to those without, possibly reflecting involvement of complement in the atherosclerotic process in RA.
Comparison of PET, MRI, and CT with pathology in a proven case of Alzheimer's disease (1986)

Positron emission tomography (PET) with fluorodeoxyglucose (FDG), magnetic resonance imaging (MRI), and CT were carried out in a patient with Alzheimer's disease 16 months before he died. At autopsy, the gross appearance of the brain correlated with MRI and CT, which showed some regional atrophy. These were much less revealing than PET, which correlated with microscopic findings of neuronal loss and proliferation of glia. In areas of moderately impaired local cerebral metabolic rate of glucose, as revealed by reduced FDG uptake, there was some gliosis, primarily around the numerous senile plaques. In areas of severe metabolic impairment, there was a profound loss of neurons, extensive gliosis, and a diminished appearance of plaques. PET-FDG is a better measure of the severity of Alzheimer's disease than MRI or CT, because it reflects the degree of neuronal pathology.
Διερεύνηση της δράσης των αναβολικών φαρμάκων στην απελευθέρωση νευρομεταβιβαστικών αμινοξέων στον υποθάλαμο του εγκεφάλου επιμυών (2002)

Η χρήση αναβολικών στεροειδών φαρμάκων για τη βελτίωση των επιδόσεων αθλητών είναι πλέον δεδομένη. Οι ενέργειες των ουσιών αυτών στο ΚΝΣ είναι άμεσες και έμμεσες σε διαφόρων τύπων νευρώνες. Από τις δράσεις αυτές παρατηρούνται σαφείς αλλαγές στη συμπεριφορά (μείωση του άγχους, αύξηση της επιθετικότητας, ευφορία και τάση για κατάχρηση). Στην παρούσα μελέτη διερευνήθηκε η επίδραση της δεκανοϊκής ναδρολόνης στη συγκέντρωση των διεγερτικών και κατασταλτικών νευροδιαβιβαστικών αμινοξέων σε πρώτη φάση σε ομογενοποιήματα πυρήνων εγκεφάλων επιμύων και σε δεύτερη σειρά πειραμάτων η συγκέντρωση των ίδιων αμινοξέων σε υπερδιήθημα οπισθίου υποθαλάμου και κάτω από διαφορετικές συνθήκες. Χρησιμοποιήθηκαν άρρενες επίμυες Wistar στους οποίους το αναβολικό χορηγήθηκε άπαξ ημερησίως σε δόση 15 mg/Kg και για χρονικό διάστημα 15, 30 και 60 ημερών. Στη συνέχεια προσδιορίστηκε η συγκέντρωση του GABA και του γλουταμινικού οξέος σε διάφορους πυρήνες ενώ ακολούθησε υπερεκχείλιση του οπισθίου υποθαλάμου και υποβολή των πειραματόζωων σε δοκιμασίες ήχου (95 dB) και πόνου (εφαρμογή σφιγκτήρα στην ουρά). Τα αμινοξέα μετρήθηκαν με υγρή χρωματογραφία υψηλής απόδοσης και φθορισμομετρικό ανιχνευτή μετά από παραγώγιση με ορθοφθαλδυαλδεϋδη. Παράλληλα τα πειραματόζωα υποβλήθηκαν και σε δοκιμασία συμπεριφοράς υπερυψωμένου σταυροειδούς λαβυρίνθου. Τα συμπεράσματα της παραπάνω μελέτης είναι ότι η δεκανοϊκή ναδρολόνη ασκεί αντιαγχώδη δράση στα πειραματόζωα, η οποία εκφράζεται με μείωση του συναισθήματος του φόβου και έτσι επαγωγή επιθετικής συμπεριφοράς. Φαίνεται ακόμη ότι επάγει συναισθήματα αμοιβής-ευχαρίστησης μέσω του υποθαλάμου και αυτό συνάδει με την τάση κατάχρησης των αναβολικών από τους αθλητές και την πιθανή φαρμακευτική εξάρτηση που προκαλεί η αγωγή με μεγάλες δόσεις αναβολικών.
Continuous observation of microstructural degradation during tensile loading of particle reinforced aluminium matrix composites (1995)

AbstractAbstractThe microstructural degradation of aluminium alloy composites by external tensile loading was continuously observed by in situ scanning electron microscopy tensile testing. The composites, which contained spherical Al2O3 and angular SiC particles, were prepared by the powder extrusion method. Some microcracks were initiated at small plastic strains after yielding in both composites by inteliace debonding and particle cracking. Angular particles generate microvoids at smaller strains than spherical particles. The microcracks do not propagate with increasing external loading because of the ductility of the matrix, but a number of new microcracks developed just before failure. Most microcracks are due to interface debonding rather than particle cracking. Many dimples on the matrix aluminium alloy are observed on some particles seen in the fracture surface, which proves that there is relatively strong bonding between the matrix and the particles in the composite produced by powder extrusion. However, part of the original surface observed on the debonded particles indicates that an incompletely bonded interface also exists in the composites.MST /3111
Modeling and Parameter Estimation of Step‐Growth Polymerization of Ethylene Glycol and 2,5‐Furandicarboxylic Acid (FDCA) Using the Method of Moments (2020)

Abstract The present work investigates the modeling of bulk step‐growth polymerization of ethylene glycol (EG) and 2,5‐furandicarboxylic acid (FDCA) for production of poly(ethylene‐2,5‐furandicarboxylate) (PEF), using the method of moments. The kinetic model is validated with experiments performed at distinct reaction temperatures and nitrogen flowrates. The polymerization process followed the well‐known two step procedure, where the direct esterification of EG and FDCA under continuous nitrogen flow is performed first, and the transesterification of produced oligomers is performed in sequence under vacuum. Kinetic and mass transfer rate parameters are estimated to describe the available experimental data. The obtained results confirmed that this polymerization can be highly limited by mass transfer constraints.
Partially-Supervised Novel Object Captioning Leveraging Context from\n Paired Data (2021)

In this paper, we propose an approach to improve image captioning solution\nfor images with novel objects that do not have caption labels in the training\ndataset. We refer to our approach as Partially-Supervised Novel Object\nCaptioning (PS-NOC). PS-NOC is agnostic to model architecture, and primarily\nfocuses on the training approach that uses existing fully paired image-caption\ndata and the images with only the novel object detection labels (partially\npaired data). We create synthetic paired captioning data for novel objects by\nleveraging context from existing image-caption pairs. We then create\npseudo-label captions for partially paired images with novel objects, and use\nthis additional data to fine-tune the captioning model. We also propose a\nvariant of SCST within PS-NOC, called SCST-F1, that directly optimizes the\nF1-score of novel objects. Using a popular captioning model (Up-Down) as\nbaseline, PS-NOC sets new state-of-the-art results on held-out MS COCO\nout-of-domain test split, i.e., 85.9 F1-score and 103.8 CIDEr. This is an\nimprovement of 85.9 and 34.1 points respectively compared to baseline model\nthat does not use partially paired data during training. We also perform\ndetailed ablation studies to demonstrate the effectiveness of our approach.\n
Formation and Structure of Transplantable Tissue Constructs Generated in Simulated Microgravity from Sertoli Cells and Neuron Precursors (2004)

Cell transplantation therapy for Parkinson's disease (PD) has received much attention as a potential treatment protocol for this neurodegenerative condition. Although there have been promising successes with this approach, it remains problematic, especially regarding the inability to provide immediate trophic support to the newly grafted cells and the inability to prevent acute and/or long-term graft rejection by the host. To address these issues of cell graftability, we have created a novel tissue construct from isolated rat Sertoli cells (SC) and the NTerra-2 immortalized human neuron precursor cell line (NT2) utilizing NASA-developed simulated microgravity technology. The two cell types were cocultured at a 1:4 (SC/NT2) ratio in the High Aspect Rotating Vessel (HARV) biochamber for 3 days, after which a disc-shaped aggregate (1-4 mm diameter) was formed. Sertoli neuron aggregated cells (SNAC) were collected by gravity sedimentation and processed either for light and electron microscopy or for fluorescent immunocytochemistry. Intra-SNAC clusters of SC and NT2 cells were identified by anti-human mitochondrial protein (huMT--specific for NT2 cells) and cholera toxin subunit B (CTb--specific for SC). There was little evidence of cell death throughout the aggregate and the absence of central necrosis, as might be expected in such a large aggregate in vitro. Ultrastructurally, SC did not express junctional modifications with NT2 cells nor with adjacent SC as is typical of SC in vivo and, in some protocols, in vitro. NT2 cells, however, showed distinct intercellular junction-like densities with adjacent NT2 cells, often defining canaliculi-like channels between the microvillus borders of the cells. The results show that the use of simulated microgravity coculture provides a culture environment suitable for the formation of a unique and viable Sertoli-NT2 (i.e., SNAC) tissue construct displaying intra-aggregate cellular organization. The structural integration of SC with NT2 cells provides a novel transplantable tissue source, which can be tested to determine if SC will suppress rejection of the grafted NT2 cells and provide for their short- and long-term trophic support in situ in the treatment of experimental PD.
Genotypic Variation and Mixtures of Lyme Borrelia in Ixodes Ticks from North America and Europe (2010)

The presence of multiple Borrelia genotypes in ticks increases the probability that a person will be infected with more than one genotype of B. burgdorferi, potentially increasing the risks of disseminated Lyme disease. Our study indicates that the genotypic diversity of Borrelia in ticks in both North America and Europe is higher then previously reported and can have potential clinical consequences.
Vemurafenib and Rituximab in Patients with Hairy Cell Leukemia Previously Treated with Moxetumomab Pasudotox (2021)

The purine nucleoside analogues cladribine and pentostatin are highly-active first-line therapeutic treatments for hairy cell leukemia (HCL), resulting in complete response rates of 80 to 90%. However, HCL patients continue to relapse, and sooner or later, most require subsequent lines of treatment. This report presents the relapsed patients with classic HCL who were treated with vemurafenib (mostly at the low dose of 240 mg twice daily for 16 weeks) combined with rituximab after the failure of several lines of therapy including cladribine with or without rituximab and moxetumomab pasudotox. Two patients achieved CR MRD (-) after combined treatment with vemurafenib and rituximab, with a hematologic response ongoing after 38 months from the end of treatment in one patient and a relapse of cytopenias occurring after 13 months in the other patient. A third patient normalized her blood counts and this hematologic response, which was not evaluated in the bone marrow at the end of treatment, was lost after 18 months. The last patient died due to infection and multi-organ failure, too early to verify response to vemurafenib. Two patients who had relapsed after vemurafenib and rituximab derived meaningful clinical benefit from retreatment with the same agents, but eventually relapsed again and started indefinite therapy with dabrafenib and trametinib with normalization of the blood counts despite heavy bone marrow infiltration in the only patient so far evaluable. The outcomes of these cases indicate that novel targeted agents, and in particular vemurafenib combined with rituximab, improve the prognosis of HCL patients, even those heavily pretreated with PNAs and moxetumomab pasudotox
Configured Grant for Ultra-Reliable and Low-Latency Communications: Standardization and Beyond (2022)

Uplink configured Grant allocation has been introduced in Third Generation Partnership Project New Radio Release 15. This is beneficial in supporting Ultra-Reliable and Low-Latency Communication for industrial communication, a key Fifth Generation mobile communication usage scenario. This scheduling mechanism enables a user with periodic traffic to transmit its data readily and bypass the control signaling entailed to scheduling requests and scheduling grants and provides low latency access. To facilitate ultra-reliable communication, the scheduling mechanism can allow users to transmit consecutive redundant transmissions in a predefined period. However, if the traffic is semi-deterministic, the current standardized configured grant allocation is not equipped to emulate the traffic as the configured grant's period is preconfigured and fixed. This article describes the recent advancements in the standardization process in Release 15 and 16 for configured grant allocation and the prospective solutions to accommodate semi-deterministic traffic behavior for configured grant allocations.
Addition von Arylisocyanaten an S‐Methyl(thiolactime) (1976)

Abstract Mit Arylisocyanaten reagiert das S‐Methyl‐1,4‐thiobutyrolactim (1) in einer (1:1)‐Addition zu N‐Aryl‐2‐methylthio‐1‐pyrrolin‐3‐carbonsäureamiden 4a,b, welche zu einer weiteren Isocyanatanlagerung befähigt sind. Dagegen addieren die S‐Methyl‐1,5‐ und S‐Methyl‐1,6‐thiolactime 7a, b die Arylisocyanate direkt am Stickstoff zu N‐Aryl‐6‐methylthio‐1,2,3,4‐tetrahydropyridin‐1‐ und N‐Aryl‐7‐methylthio‐2,3,4,5‐tetrahydro‐1 H‐azepin‐1‐carbonsaure‐amiden 8a‐d. Mit 8a und Phenylisocyanat tritt erst unter verschärften Bedingungen eine weitere Reaktion zum Pyrido[2,3‐d]pyrimidin 9 ein. Die IR‐ und 1 H‐NMR‐Daten der erhaltenen Verbindungen werden beschrieben.
Discovery of a Potent (4R,5S)-4-Fluoro-5-methylproline Sulfonamide Transient Receptor Potential Ankyrin 1 Antagonist and Its Methylene Phosphate Prodrug Guided by Molecular Modeling (2018)

Transient receptor potential ankyrin 1 (TRPA1) is a non-selective cation channel expressed in sensory neurons where it functions as an irritant sensor for a plethora of electrophilic compounds and is implicated in pain, itch, and respiratory disease. To study its function in various disease contexts, we sought to identify novel, potent, and selective small-molecule TRPA1 antagonists. Herein we describe the evolution of an N-isopropylglycine sulfonamide lead (1) to a novel and potent (4 R,5 S)-4-fluoro-5-methylproline sulfonamide series of inhibitors. Molecular modeling was utilized to derive low-energy three-dimensional conformations to guide ligand design. This effort led to compound 20, which possessed a balanced combination of potency and metabolic stability but poor solubility that ultimately limited in vivo exposure. To improve solubility and in vivo exposure, we developed methylene phosphate prodrug 22, which demonstrated superior oral exposure and robust in vivo target engagement in a rat model of AITC-induced pain.