gebhart/patrepeval huggingface dataset:
Manual of Coagulation Disorders (2001)

1. Mechanisms of Coagulation 2. The Biological Basis for Routine Coagulation Testing 3. An Overview of Thrombotic Disorders and Their Treatment 4. Venous Thromboembolism 5. Anticoagulant Therapy 6. Arterial Thrombosis 7. Antiplatelet Agents 8. Thrombolytic Therapy 9. Lupus Anticoagulants, Antiphospholipid Antibodies, and the Antiphospholipid Syndrome 10. Hypercoagulable Sates 11. Thrombocytosis 12. Thrombotic Thrombocytotic Purpura and the Hemolytic-Uremic Syndrome 13. An Overview of Hemorrhagic Disorders and Their Treatment 14. Thrombocytopenia 15. Qualitative Platelet Disorders 16. Von Willebrand Disease 17. Hemophilia and Other Coagulation Factor Deficiencies 18. Coagulation Factor Inhibiors 19. Acquired Coagulopathies
Role of the CLOCK Protein in the Mammalian Circadian Mechanism (1998)

The mouse Clock gene encodes a bHLH-PAS protein that regulates circadian rhythms and is related to transcription factors that act as heterodimers. Potential partners of CLOCK were isolated in a two-hybrid screen, and one, BMAL1, was coexpressed with CLOCK and PER1 at known circadian clock sites in brain and retina. CLOCK-BMAL1 heterodimers activated transcription from E-box elements, a type of transcription factor-binding site, found adjacent to the mouse per1 gene and from an identical E-box known to be important for per gene expression in Drosophila. Mutant CLOCK from the dominant-negative Clock allele and BMAL1 formed heterodimers that bound DNA but failed to activate transcription. Thus, CLOCK-BMAL1 heterodimers appear to drive the positive component of per transcriptional oscillations, which are thought to underlie circadian rhythmicity.
Stacked planar optics: an application of the planar microlens (1982)

In this paper we present a new development of the distributed-index planar microlens of 2.5-3-mm focal length and 0.15 N.A. and also show that it is usable with optical components in fiber communications. We then propose a concept of stacked planar optics consisting of a stack of arrayed planar microlenses and other optical components. From this configuration a 2-D array of optical devices is monolithically available, and many discrete components can be separated from the array. An optical tap array has been fabricated as an example of stacked planar optics.
High-Dose Chemotherapy plus Autologous Bone Marrow Transplantation for Metastatic Breast Cancer (2000)

In this issue of the Journal, Stadtmauer et al. present the results of a clinical trial in which conventional-dose chemotherapy was compared with high-dose chemotherapy plus autologous bone marrow transplantation (hematopoietic stem-cell rescue) in patients with metastatic breast cancer.1 In this trial, 553 women with previously untreated metastatic or locally recurrent breast cancer were initially treated with conventional multidrug chemotherapy; patients who had a response, according to predefined objective criteria, were then randomly assigned to receive either maintenance chemotherapy at standard doses or high-dose chemotherapy plus an autologous bone marrow transplant. In this randomization phase, a total of 199 women . . .
Microbubbles and ultrasound: from diagnosis to therapy (2004)

The development of ultrasound contrast agents, containing encapsulated microbubbles, has increased the possibilities for diagnostic imaging. Ultrasound contrast agents are currently used to enhance left ventricular opacification, increase Doppler signal intensity, and in myocardial perfusion imaging. Diagnostic imaging with contrast agents is performed with low acoustic pressure using non-linear reflection of ultrasound waves by microbubbles. Ultrasound causes bubble destruction, which lowers the threshold for cavitation, resulting in microstreaming and increased permeability of cell membranes. Interestingly, this mechanism can be used for delivery of drugs or genes into tissue. Microbubbles have been shown to be capable of carrying drugs and genes, and destruction of the bubbles will result in local release of their contents. Recent studies demonstrated the potential of microbubbles and ultrasound in thrombolysis. In this article, we will review the recent advances of microbubbles as a vehicle for delivery of drugs and genes, and discuss possible therapeutic applications in thrombolysis.
Effect of Nanocrystallite Morphology on the Metastable Tetragonal Phase Stabilization in Zirconia (2002)

We synthesize, for the first time, using sol−gel technique and without doping any trivalent impurities, monodispersed, spherical ZrO2 particles in size range of ∼500−600 nm, exhibiting metastable tetragonal crystal structure at room temperature. It is revealed using high-resolution transmission electron microscopy that “hard-aggregates” forming tendency of ZrO2 nanocrystallites of size ∼45 nm is responsible for stabilizing the high-temperature metastable tetragonal phase, at room temperature, within large sized (∼500−600 nm) undoped ZrO2 particles.
Definition and natural history of Lennox‐Gastaut syndrome (2011)

Lennox-Gastaut syndrome (LGS) is a rare epileptic encephalopathy with a peak age of onset of 3-5 years of age. Reported prevalence rates for LGS vary widely from 1-10% of all childhood epilepsies. Incidence rates are much lower. LGS is characterized by intractable, multiple, generalized seizure types and an interictal electroencephalogram showing bursts of slow spike-and-wave, paroxysmal bursts of generalized polyspikes, and a slow background. All patients have tonic seizures during sleep that may be subtle, and nearly all have treatment-resistant, lifelong epilepsy. Cognitive stagnation and behavioral problems are seen in almost all patients and lead to a life of dependency. The differential diagnosis includes other symptomatic generalized epilepsies and pseudo-Lennox syndrome. Misdiagnosis is common. Children and adults with LGS have an enormous impact on their families, and efforts to improve the quality of life for these patients are complex.
Structure/Nuclease Activity Relationships of DNA Cleavers Based on Cationic Metalloporphyrin−Oligonucleotide Conjugates (1996)

The covalent attachment of a managanese-tris(methylpyridiniumyl)porphyrin entity to an antisense oligonucleotide allowed sequence-selective oxidative cleavage of DNA when the metalloporphyrin was activated by potassium monopersulfate (KHSO5). We prepared several structurally modified metallo-porphyrin-oligonucleotide conjugates in order to find out the most efficient compound for in vitro DNA cleavage. The nature and the length of the tether were modulated, the metalloporphyrin entity was modified (metal, ligand), and different ways of activation of the metalloporphyrin were assayed. We noticed that the location of the peptidic bond within the linker could greatly affect the cleavage efficiency of the different conjugates. We showed that the most efficient conjugate for oxidative DNA cleavage was a manganese tetracationic porphyrin-oligonucleotide compound. When the metalloporphyrin moiety was activated by a reducing agent in the presence of molecular oxygen, DNA cleavage was efficient at suitable concentrations of the reducing agent, in order to avoid the reduction of the activated DNA cleaver, a putative high-valent metal-oxo species, by the excess of reducing agent.
A calcitonin gene-related peptide receptor antagonist prevents the development of tolerance to spinal morphine analgesia (1996)

Tolerance to morphine analgesia is believed to result from a neuronal adaptation produced by continuous drug administration, although the precise mechanisms involved have yet to be established. Recently, we reported selective alterations in rat spinal calcitonin gene-related peptide (CGRP) markers in morphine-tolerant animals. In fact, increases in CGRP-like immunostaining and decrements in specific [125]hCGRP binding in the superficial laminae of the dorsal horn were correlated with the development of tolerance to the spinal antinociceptive action of morphine. Other spinally located peptides such as substance P, galanin, and neuropeptide Y were unaffected. Thus, the major goal of the present study was to investigate whether the development of tolerance to spinally infused morphine could be modulated by the blockade of dorsal horn CGRP receptors using the potent CGRP antagonist hCGRP(8-37). Indeed, cotreatments with hCGRP(8-37) prevented, in a dose-dependent manner, the development of tolerance to morphine-induced analgesia in both the rat tail-flick/tail-immersion and paw-pressure tests. Moreover, alterations in spinal CGRP markers seen in morphine-tolerant animals were not observed after a coadministration of morphine and hCGRP(8-37). These results demonstrate the existence of specific interaction between CGRP and the development of tolerance to the spinal antinociceptive effects of morphine. They also suggest that CGRP receptor antagonists could become useful adjuncts in the treatment of pain and tolerance to the antinociceptive effects of morphine.
The bimodal regulation of epidermal growth factor signaling by human Sprouty proteins (2002)

Signal transduction through epidermal growth factor receptors (EGFRs) is essential for the growth and development of multicellular organisms. A genetic screen for regulators of EGFR signaling has led to the identification of Sprouty, a cell autonomous inhibitor of EGF signaling that is transcriptionally induced by the pathway. However, the molecular mechanisms by which Sprouty exerts its antagonistic effect remain largely unknown. Here we have used transient expression in human cells to investigate the functional properties of human Sprouty (hSpry) proteins. Ectopically expressed full-length hSpry1 and hSpry2 induce the potentiation of EGFR-mediated mitogen-activated protein (MAP) kinase activation. In contrast, truncation mutants of hSpry1 and hSpry2 containing the highly conserved carboxyl-terminal cysteine-rich domain inhibit EGF-induced MAP kinase activation. The potentiating effect of the full-length hSpry2 proteins on EGF signaling is mediated by the amino-terminal domain and results from the sequestration of c-Cbl, which in turn leads to the inhibition of EGFR ubiquitination and degradation. These results indicate that hSpry2 can function both as a negative and positive regulator of EGFR-mediated MAP kinase signaling in a domain-dependent fashion. A dual function of this kind could provide a mechanism for achieving proper balance between the activation and repression of EGFR signaling.
JAVADAPTOR: unrestricted dynamic updates of Java applications (2012)

In dieser Arbeit wird mit JAVADAPTOR ein Ansatz präsentiert, der die statisch getypte Programmiersprache Java um die Möglichkeit erweitert, Programme zur Laufzeit und ohne die genannten Einschränkungen zu aktualisieren. Das vorgestellte Konzept kombiniert das schemaverändernde Nachladen von Klassen mit Referenzaktualisierungen auf der Basis von Java HotSwap, Containern und Proxies. Zentrale Beiträge der Arbeit sind detaillierte Beschreibungen der Konzepte und deren Implementierung, sowie der Nachweis der Praxvistauglichkeit der Lösung anhand verschiedener Fallstudien. Weiterhin wird untersucht, ob die präsentierte Lösung Einschränkungen bezüglich Flexibilität, Performanz, Plattform, Programmarchitektur oder Änderungsgranularität unterliegt.
65nm OPC and design optimization by using simple electrical transistor simulation (2005)

In the context of 65nm logic technology where gate CD control budget requirements are below 5nm, it is mandatory to properly quantify the impact of the 2D effects on the electrical behavior of the transistor [1,2]. This study uses the following sequence to estimate the impact on transistor performance: 1) A lithographic simulation is performed after OPC (Optical Proximity Correction) of active and poly using a calibrated model at best conditions. Some extrapolation of this model can also be used to assess marginalities due to process window (focus, dose, mask errors, and overlay). In our case study, we mainly checked the poly to active misalignment effects. 2) Electrical behavior of the transistor (Ion, Ioff, Vt) is calculated based on a derivative spice model using the simulated image of the gate as an input. In most of the cases Ion analysis, rather than Vt or leakage, gives sufficient information for patterning optimization. We have demonstrated the benefit of this approach with two different examples: -design rule trade-off : we estimated the impact with and without misalignment of critical rules like poly corner to active distance, active corner to poly distance or minimum space between small transistor and big transistor. -Library standard cell debugging: we applied this methodology to the most critical one hundred transistors of our standard cell libraries and calculate Ion behavior with and without misalignment between active and poly. We compared two scanner illumination modes and two OPC versions based on the behavior of the one hundred transistors. We were able to see the benefits of one illumination, and also the improvement in the OPC maturity.
High-resolution kinetics of transferrin acidification in BALB/c 3T3 cells: exposure to pH 6 followed by temperature-sensitive alkalinization during recycling. (1987)

The kinetics of acidification of diferric human transferrin in BALB/c mouse 3T3 cells were determined by flow cytometry using a modification of the fluorescein-rhodamine fluorescence ratio technique. For cells labeled at 0 degrees C and warmed to 37 degrees C, the minimum pH observed was 6.1 +/- 0.2, occurring 5 min after warmup. This step was followed by a slower alkalinization to the pH of the external medium, occurring with a half-time of 5 min. Warmup to 24 degrees C or 17 degrees C resulted in slowing of the time of onset of acidification such that the minimum pH was 6.3 +/- 0.2, attained 15 and 25 min after warmup, respectively; the alkalinization step was completely blocked. The limited acidification observed for transferrin corresponds to the initial phase of acidification normally observed for other (nonrecycled) ligands. Since transferrin is not further acidified, the results confirm the existence of two phases of acidification during endocytosis. Measurements of transferrin dissociation at neutral pH after exposure to mildly acidic pH support the conclusion that the transferrin cycle may be completed without exposure of transferrin to a pH below 6. The mildly acidic pH of the endocytic compartments involved in recycling may play a role in regulating enzymatic processing of endocytosed material.
[Treatment of sphenopalatine ganglion neuralgia]. (1989)

The Sphenopalatine neuralgia of the ganglion is characterized for a throbbing pain mostly unilateral encircling the orbit and occasionally extended to the neighborhood. A vegetative component hydrorrhea, sneezing crisis and abnormal lacrimation is associated. The ideal therapy, giving excellent results, is the iontophoresis of the ganglion, which technic was published years ago by F. Barceló.
Interplay between PKCδ and Sp1 on Histone Deacetylase Inhibitor-Mediated Epstein-Barr Virus Reactivation (2010)

Epstein-Barr virus (EBV) undergoes latent and lytic replication cycles, and its reactivation from latency to lytic replication is initiated by expression of the two viral immediate-early transactivators, Zta and Rta. In vitro, reactivation of EBV can be induced by anti-immunoglobulin, tetradecanoyl phorbol acetate, and histone deacetylase inhibitor (HDACi). We have discovered that protein kinase C delta (PKCδ) is required specifically for EBV reactivation by HDACi. Overexpression of PKCδ is sufficient to induce the activity of the Zta promoter (Zp) but not of the Rta promoter (Rp). Deletion analysis revealed that the ZID element of Zp is important for PKCδ activation. Moreover, the Sp1 putative sequence on ZID is essential for PKCδ-induced Zp activity, and the physiological binding of Sp1 on ZID has been confirmed. After HDACi treatment, activated PKCδ can phosphorylate Sp1 at serine residues and might result in dissociation of the HDAC2 repressor from ZID. HDACi-mediated HDAC2-Sp1 dissociation can be inhibited by the PKCδ inhibitor, Rotterlin. Furthermore, overexpression of HDAC2 can suppress the HDACi-induced Zp activity. Consequently, we hypothesize that HDACi induces PKCδ activation, causing phosphorylation of Sp1, and that the interplay between PKCδ and Sp1 results in the release of HDAC2 repressor from Zp and initiation of Zta expression.
Neurovascular dysfunction in diabetic rats. Potential contribution of autoxidation and free radicals examined using transition metal chelating agents. (1995)

Oxygen free radical activity is elevated in diabetes mellitus and has been implicated in the etiology of vascular complications. Recent studies have shown that impaired perfusion of nerve endoneurium is a major cause of nerve fiber dysfunction in experimental diabetes. Free radical scavenger treatment prevents the development of nerve conduction abnormalities in diabetic rats. In vitro experiments suggest that autoxidation reactions of glucose, catalyzed by free transition metal ions, are a potential source of free radicals in diabetes. We investigated whether chronic treatment with deferoxamine and trientine, transition metal chelating agents which can prevent autoxidation, could correct nerve conduction and blood flow changes in streptozotocin-diabetic rats. A 20% reduction in sciatic nerve motor conduction velocity after 2 mo diabetes was 90% ameliorated by 2 wk of treatment with deferoxamine or trientine. Sciatic endoneurial nutritive blood flow was 45% reduced by diabetes, but was completely corrected by treatment. In contrast, transition metal chelation had no effect on blood flow or conduction velocity in nondiabetic rats. Thus, the data support the hypothesis that increased free radical activity by glucose autoxidation as a result of impaired transition metal handling is a major cause of early neurovascular deficits in diabetes.
The Nucleotide Sequence of an Equine Herpesvirus 4 Gene Homologue of the Herpes Simplex Virus 1 Glycoprotein H Gene (1990)

The equine herpesvirus 4 (EHV-4) gene glycoprotein H (gH) gene homologue was localized by virtue of the conserved genomic position of this gene throughout members of the herpesvirus family. The gene maps immediately downstream of the thymidine kinase gene at approximately 0.49 to 0.51 map units within genomic fragment BamH1 C. The EHV-4 gH primary translation product is predicted to be a polypeptide of Mr 94,100, 855 amino acids long, which possesses features characteristic of a membrane glycoprotein, namely an N-terminal signal sequence, a large hydrophilic domain containing 11 putative N-linked glycosylation sites, a C-terminal transmembrane domain, and a charged cytoplasmic tail. Comparison to other herpesvirus glycoproteins revealed identities of 85%, 26% and 32% with the gH counterparts of the alphaherpesviruses EHV-1, herpes simplex virus 1 and varicella-zoster virus, respectively, and of 17% and 18% with those of human cytomegalovirus, herpesvirus saimiri and Epstein-Barr virus. The EHV-4 gH exhibits features previously reported to be conserved throughout the gH polypeptides of herpesviruses of all three subgroups. A region of direct repeat elements and a possible origin of DNA replication are located immediately downstream of the gH gene.
Gaucher disease and the synucleinopathies: refining the relationship (2012)

Gaucher disease (OMIM 230800, 230900, 231000), the most common lysosomal storage disorder, is due to a deficiency in the enzyme glucocerebrosidase. Gaucher patients display a wide spectrum of clinical presentation, with hepatosplenomegaly, haematological changes, and orthopaedic complications being the predominant symptoms. Gaucher disease is classified into three broad phenotypes based upon the presence or absence of neurological involvement: Type 1 (non-neuronopathic), Type 2 (acute neuronopathic), and Type 3 (subacute neuronopathic). Nearly 300 mutations have been identified in Gaucher patients, with the majority being missense mutations. Though studies of genotype-to-phenotype correlations have revealed significant heterogeneity, some consistent patterns have emerged to inform prognostic and therapeutic decisions. Recent research has highlighted a potential role for Gaucher disease in other comorbidities such as cancer and Parkinson's Disease. In this review, we will examine the potential relationship between Gaucher disease and the synucleinopathies, a group of neurodegenerative disorders characterized by the development of intracellular aggregates of α-synuclein. Possible mechanisms of interaction will be discussed.
The role of thromboxane in two-kidney, one-clip Goldblatt hypertension in rats (1989)

Impaired contralateral kidney (CLK) function is important in the maintenance of hypertension in the two-kidney, one-clip (2K, 1C) Goldblatt rat model. Since glomerular filtration rate (GFR) is influenced by the products of arachidonic acid metabolism, we investigated the potential role of eicosanoids as mediators of impaired CLK pressure-volume regulation. At 4 wk following right renal artery clipping, GFR of hypertensive rats was significantly reduced. This decrease was due to the fixed reduction in GFR of the clipped kidney and failure of the CLK to increase its GFR. Thromboxane (Tx) production by isolated perfused CLK was significantly elevated, whereas prostacyclin production remained unchanged. Furthermore, CLK GFR was inversely proportional to Tx production. Treatment of 4-wk hypertensive animals with either the Tx synthase inhibitor UK-38,485 or the Tx receptor antagonist GR 32191 produced a significant increase in CLK GFR. In addition, treatment with either the Tx synthase inhibitor or the Tx receptor antagonist significantly reduced systemic blood pressure. Thus, in this 2K, 1C model of hypertension, increased renal Tx production prevents functional hypertrophy of the contralateral kidney. As a result, CLK pressure-volume regulation is impaired and systemic hypertension is maintained. Furthermore, Tx antagonists restore CLK function and acutely lower systemic blood pressure. Therefore, increased renal Tx production by the CLK appears to be an important mediator of hypertension in the 2K, 1C model.
High-Speed GeSi Electroabsorption Modulator on the SOI Waveguide Platform (2013)

Following significant research and development work over the past few years, silicon photonics has become a promising candidate to provide low-power, low-cost, and high-speed photonic links for telecommunication, data communication, and interconnect applications. A high-speed optical modulator is one of the critical components for these links. In this paper, we report on our recent progress in the development of a GeSi electro-absorption (EA) modulator based on the Franz-Keldysh effect (FKE) integrated in a 3-μm silicon-on-insulator (SOI) platform. We first discuss the FKE in GeSi, and describe the EA modulator device design and fabrication. We then report on the performance of the fabricated device. Finally, we describe the monolithic integration of four modulators with a four channel wavelength division multiplexing (WDM) echelle grating to demonstrate a 112 Gbit/s (4 × 28 Gbit/s) WDM transmitter chip. This chip establishes silicon photonics as an enabling technology for low-power and low-cost data transmission applications.