gebhart/patrepeval huggingface dataset:
Experimental Demonstration of Tunable Directional Scattering of Visible Light from All-Dielectric Asymmetric Dimers (2017)

Due to the presence of strong magnetic resonances, high refractive index dielectric nanoantennnas have shown the ability to expand the methods available for controlling electromagnetic waves in the subwavelength region. In this work, we experimentally demonstrate that an asymmetric dielectric dimer made of silicon can lead to highly directional scattering depending on the excitation wavelength, due to the interference of the excited magnetic resonances. A back focal plane imaging system combined with a prism coupling technique enables us to explore the scattering profile parallel to the substrate. The directivity of scattering along the substrate is high enough to produce selective guiding of light along the substrate. These results showing tunable control of directional scattering will encourage the realization of novel optical applications, such as optical nanocircuitry.
Methods for Forming Human Microvascular Tubes In Vitro and Measuring Their Macromolecular Permeability (2010)

This chapter describes a protocol for forming open endothelial tubes in vitro and quantifying their permeability to macromolecules. These tubes consist of confluent monolayers of human microvascular endothelial cells in perfused microfluidic collagen gels. The cylindrical geometry of the tubes mimics the shape of microvessels in vivo; it allows simultaneous and/or repeated measurements of permeability coefficients and detection of focal leaks. We have used these in vitro models to test the effects of agonists on microvascular permeability and are developing arrays of microvascular tubes to enable large-scale testing.
Bestimmungsmethoden für Erythropoietin [Assay methods for erythropoietin] (1989)

The aim of this contribution is to briefly characterize the assays available for the quantitation of erythropoietin (EPO). The radioimmunological determination of EPO has gained priority for routine and screening measurements. The in vivo bioassay is the most reliable assay for biologic EPO activity. In vitro bioassays should be limited to situations in which radioimmunoassays are not available and for which in vivo bioassays are too insensitive.
Independent expression of human alpha or beta platelet-derived growth factor receptor cDNAs in a naive hematopoietic cell leads to functional coupling with mitogenic and chemotactic signaling pathways. (1989)

Distinct genes encode alpha and beta platelet-derived growth factor (PDGF) receptors that differ in their abilities to be triggered by three dimeric forms of the PDGF molecule. We show that PDGF-receptor mitogenic function can be reconstituted in a naive hematopoietic cell line by introduction of expression vectors for either alpha or beta PDGF receptor cDNAs. Thus, each receptor is independently capable of coupling with mitogenic signal-transduction pathways inherently present in these cells. Activation of either receptor also resulted in chemotaxis, alterations in inositol lipid metabolism, and mobilization of intracellular Ca2+. The magnitude of these functional responses correlated well with the binding properties of the different PDGF isoforms to each receptor. Thus, availability of specific PDGF isoforms and relative expression of each PDGF-receptor gene product are major determinants of the spectrum of known PDGF responses.
A phase I, first-in-human, open-label, dose-escalation, safety, pharmacokinetic, and pharmacodynamic study of oral TP-1287 administered daily to patients with advanced solid tumors. (2020)

3611 Background: TP-1287 is a an orally bioavailable phosphate prodrug of alvocidib, a cyclin dependent kinase 9 (CDK9) inhibitor. TP-1287 exhibits potent inhibition of intracellular kinases including CDK9. Inhibition of CDK9 leads to downregulation of the BCL-2 family member, MCL-1, which in turn inhibits tumor growth in preclinical animal models of prostate, breast, and lung carcinomas. Methods: This is a multicenter, Phase 1, dose escalation study using a standard 3+3 design with a modified Fibonacci scheme to examine the safety and clinical activity of TP-1287 in patients with advanced solid tumors. Patients will be added at the maximum tolerated dose (i.e. expansion cohort) to test TP-1287 as a single agent in patients with castrate resistant prostate cancer. Results: Twenty-two patients who were enrolled between December 2018 and January 2020 received a range of doses from 1 mg QD to 11 mg BID over 7 cohorts. Data are available for 20 patients as of the data cutoff date. TP-1287 plasma PK C max and AUC increased in near linear fashion over cohorts 1 thru 6, reaching 80 ng/mL and 499.3 ng*h/mL in cohort 6 for C max and AUC, respectively. TP-1287 treatment resulted in dose-dependent reductions of phospho-RNA Pol II, consistent with CDK9 inhibition, as measured by a flow cytometric assay assessing pharmacodynamic changes in phosphorylation state in PBMCs. The most frequently observed Grade 3 AE was unrelated anemia in 2 patients. All other events of Grade 3 (9 events/7 patients) and Grade 4 (1 event/seizure with new CNS mets) were unlikely related or unrelated. Clinical benefit was seen in one sarcoma patient with PR (15+cycles), one RCC patient with SD (7+cycles) and 2 bladder cancer patients with SD (6 and 8 cycles). Conclusions: These findings suggest that TP-1287 is tolerated as a monotherapy in patients with heavily pretreated, relapsed, refractory solid tumors and further clinical development in selected indications is warranted. Clinical trial information: NCT03298984 .
Very Large Breathing Effect in the First Nanoporous Chromium(III)-Based Solids: MIL-53 or CrIII(OH)·{O2C−C6H4−CO2}·{HO2C−C6H4−CO2H}x·H2Oy (2002)

The first three-dimensional chromium(III) dicarboxylate, MIL-53as or Cr(III)(OH) x [O(2)C-C(6)H(4)-CO(2)].[HO(2)C-C(6)H(4)-CO(2)H](0.75), has been obtained under hydrothermal conditions (as: as-synthesized). The free acid can be removed by calcination giving the resulting solid, MIL-53ht or Cr(III)(OH) x [O(2)C-C(6)H(4)-CO(2)]. At room temperature, MIL-53ht adsorbs atmospheric water immediately to give Cr(III)(OH) x [O(2)C-C(6)H(4)-CO(2)] x H(2)O or MIL-53lt (lt: low-temperature form, ht: high-temperature form). Both structures, which have been determined by using X-ray powder diffraction data, are built up from chains of chromium(III) octahedra linked through terephthalate dianions. This creates a three-dimensional structure with an array of one-dimensional large pore channels filled with free disordered terephthalic molecules (MIL-53as) or water molecules (MIL-53lt); when the free molecules are removed, this leads to a nanoporous solid (MIL-53ht) with a Langmuir surface area over 1500 m(2)/g. The transition between the hydrated form (MIL-53lt) and the anhydrous solid (MIL-53ht) is fully reversible and followed by a very high breathing effect (more than 5 A), the pores being clipped in the presence of water molecules (MIL-53lt) and reopened when the channels are empty (MIL-53ht). The thermal behavior of the two solids has been investigated using TGA and X-ray thermodiffractometry. The sorption properties of MIL-53lt have also been studied using several organic solvents. Finally, magnetism measurements performed on MIL-53as and MIL-53lt revealed that these two phases are antiferromagnetic with Néel temperatures T(N) of 65 and 55 K, respectively. Crystal data for MIL-53as is as follows: orthorhombic space group Pnam with a = 17.340(1) A, b = 12.178(1) A, c = 6.822(1) A, and Z = 4. Crystal data for MIL-53ht is as follows: orthorhombic space group Imcm with a = 16.733(1) A, b = 13.038(1) A, c = 6.812(1) A, and Z = 4. Crystal data for MIL-53lt is as follows: monoclinic space group C2/c with a = 19.685(4) A, b = 7.849(1) A, c = 6.782(1) A, beta = 104.90(1) degrees, and Z = 4.
Two models of multiple sclerosis: Experimental allergic encephalomyelitis (EAE) and theiler's murine encephalomyelitis virus (TMEV) infection. A pathological and immunological comparison (1995)

Theiler's murine encephalomyelitis virus (TMEV) infection and experimental allergic encephalomyelitis (EAE) are considered among the best models of human multiple sclerosis (MS). In both models, clinical disease is characterized by paralysis, while pathological changes consist of inflammatory demyelination. In both models there is a genetic influence on susceptibility/resistance to the development of disease. This has been thoroughly studied in TMEV infection, and it has been found to depend on both major histocompatibility complex (MHC) and non-MHC genes. At least four genes have been so far identified. Because of this genetic influence, some strains of mice are more susceptible to both clinical and pathological changes than others, and susceptibility appears to best correlate with the ability of a certain murine strain to develop a delayed-type hypersensitivity (DTH) response to viral antigens. We have also observed that even among mice which are equally susceptible clinically, striking differences may be seen under pathological examination. These consist of different gradients of severity of inflammation, particularly in regards to the macrophage component. There is an inverse relationship between the number of macrophages, and their length of stay in the CNS, and the ability of mice to remyelinate their lesions. The most severe lesions are in SJL/J mice, and remyelination in this strain is extremely poor. The least severe lesions in terms of macrophage invasion are in strains such as NZW and RIIIS/J, and these are able to remyelinate lesions very successfully. Murine chronic relapsing EAE (CR-EAE) shows pathological changes in many ways similar to those in TMEV-infected SJL/J mice, although less severe in terms of degrees of macrophage infiltration and tissue destruction. Mice with CR-EAE have a correspondingly limited ability to remyelinate their lesions. In both models the pathology appears to be mediated through a DTH response. However, while in EAE the DTH response is clearly against neuroantigens, the response in TMEV infection is against the virus itself. The end result in both models would be that of myelin destruction through a lymphotoxin-cytokine-mediated mechanism. The importance of the DTH response in both models is well illustrated by the effects of tolerance induction in EAE and TMEV infection to neuroantigens and virus, respectively. These are important models of human MS, since the current hypothesis is that a viral infection early in life, on the appropriate genetic background, may trigger a secondary misdirected immune response which could be directed either against myelin antigens and/or possible persistent virus(es).
Neuroprotection by Complement (C1) Inhibitor in Mouse Transient Brain Ischemia (2003)

The authors investigated the effect of the C1 inhibitor (C1-INH), the only known inhibitor of complement C1, in a murine model of transient focal ischemia. Ischemia was induced by intraluminal occlusion of the middle cerebral artery. After 2 hours, reperfusion was produced by removing the nylon monofilament occluding the artery. The effect of 15 U C1-INH (intravenously) was evaluated in terms of general and focal neurologic deficits, ischemic volume, neutral red staining (to identify the brain areas subject to ischemic damage), and glial fibrillary acidic protein immunoreactivity (to show astrocytic response). Forty-eight hours after ischemia, C1-INH significantly improved general and focal deficits by 36% and 54%, respectively, and significantly reduced infarct volume (CI-INH, 6.69% +/- 2.93%; saline, 24.24% +/- 8.24%) of total brain. Neutral red staining further showed the strong protective effect of C1-INH in cortex, hippocampus, and striatum. Astrocyte activation induced by ischemia was not affected by C1-INH. These findings show that C1-INH displayed a potent neuroprotective action by effectively reducing ischemia-reperfusion injury.
Genetic alterations of the c-erbB-2 oncogene occur frequently in tubular adenocarcinoma of the stomach and are often accompanied by amplification of the v-erbA homologue. (1988)

We analyzed for alterations of the c-erbB-2 oncogene in 35 human stomach cancers and 8 cell lines derived from human stomach cancer. Amplification of c-erbB-2 was found in approximately 40% (5/13) of the tubular adenocarcinomas of the stomach examined, including 4 of 10 fresh tumors and one of 3 cell lines, but not in other histological types of stomach cancer examined (0/30), including 25 fresh tumors and 5 cell lines. This result strongly suggests that amplification of c-erbB-2 occurs frequently in tubular carcinomas in stomach cancer. Rearrangement of c-erbB-2 was also detected in one tubular adenocarcinoma. The rearranged fragment carried the 3' half, but not the 5' sequence, of the c-erbB-2 gene. Furthermore, one of the cellular homologues of v-erbA was amplified in 3 of 4 fresh tumors carrying the amplified c-erbB-2 gene. Both c-erbB-2 and the v-erbA homologue were expressed in all the stomach cancer cell lines tested.
Studies of Surface Coverage and Orientation of DNA Molecules Immobilized onto Preformed Alkanethiol Self-Assembled Monolayers (2000)

DNA molecules are attached onto carboxylate-terminated alkanethiol self-assembled monolayers (SAMs) preformed at gold surfaces via the N-hydroxysulfosuccinimide (NHS)/1-(3-(dimethylamino)propyl)-3-ethylcarbodiimide hydrochloride (EDC) cross-linking reaction. Cyclic voltammetry, quartz crystal microbalance (QCM), and atomic force microscopy (AFM) were used to probe the surface coverage and molecular orientation of the immobilized DNA molecules. The DNA attachment is attributed to the formation of amide bond between the carboxylate groups and the amino groups on the DNA bases since the possibility of nonspecific adsorption of DNA onto preformed SAMs or NHS ester monolayers was studied and excluded. Our voltammetric results indicate a significant blockage of the sites originally available in the alkanethiol SAMs for facile heterogeneous electron transfer by the attached DNA molecules. QCM provided a semiquantitative measurement of the amount of immobilized DNA. The AFM images, for the first time, revealed that relatively ordered DNA films can be formed in the covalent attachment with DNA molecules stretched by the underlying terminal carboxylate groups of the SAMs. However, certain fragmentation appears to have occurred upon immobilization. The fragmentation is probably due to the strong interaction between the DNA molecules and the carboxylate groups whose spatial distribution does not fit perfectly well with the separation and distribution of the amino groups on the bases within the DNA double helix.
The effects of substitute multisensory feedback on task performance and the sense of presence in a virtual reality environment (2018)

Objective and subjective measures of performance in virtual reality environments increase as more sensory cues are delivered and as simulation fidelity increases. Some cues (colour or sound) are easier to present than others (object weight, vestibular cues) so that substitute cues can be used to enhance informational content in a simulation at the expense of simulation fidelity. This study evaluates how substituting cues in one modality by alternative cues in another modality affects subjective and objective performance measures in a highly immersive virtual reality environment. Participants performed a wheel change in a virtual reality (VR) environment. Auditory, haptic and visual cues, signalling critical events in the simulation, were manipulated in a factorial design. Subjective ratings were recorded via questionnaires. The time taken to complete the task was used as an objective performance measure. The results show that participants performed best and felt an increased sense of immersion and involvement, collectively referred to as 'presence', when substitute multimodal sensory feedback was provided. Significant main effects of audio and tactile cues on task performance and on participants' subjective ratings were found. A significant negative relationship was found between the objective (overall completion times) and subjective (ratings of presence) performance measures. We conclude that increasing informational content, even if it disrupts fidelity, enhances performance and user's overall experience. On this basis we advocate the use of substitute cues in VR environments as an efficient method to enhance performance and user experience.
Insulin receptor substrate-2 gene polymorphism: is it associated with endometrial cancer? (2010)

These results suggest that IRS-2 G1057D polymorphism may be associated with endometrial cancer.
Inhibition of a Plasmodium vinckei cysteine proteinase cures murine malaria. (1993)

Intraerythrocytic malaria parasites degrade hemoglobin as a principal source of amino acids for parasite protein synthesis. We have previously identified a Plasmodium falciparum trophozoite cysteine proteinase as a putative hemoglobinase and shown that specific inhibitors of this proteinase block the hydrolysis of globin and the development of cultured parasites. We now show that the murine malaria parasite Plasmodium vinckei has an analogous cysteine proteinase with similar biochemical properties to the P. falciparum proteinase, including an acid pH optimum, a preference for the peptide proteolytic substrate benzyloxycarbonyl (Z)-Phe-Arg-7-amino-4-methylcoumarin, and nonomolar inhibition by seven peptide fluoromethyl ketone proteinase inhibitors. Thus, P. vinckei offers a model system for the in vivo testing of the antimalarial properties of cysteine proteinase inhibitors. One of the proteinase inhibitors studied, morpholine urea (Mu)-Phe-Homophenylalanine (HPhe)-CH2F strongly inhibited the P. vinckei cysteine proteinase in vitro and rapidly blocked parasite cysteine proteinase activity in vivo. When administered four times a day for 4 d to P. vinckei-infected mice, Mu-Phe-HPhe-CH2F elicited long-term cures in 80% of the treated animals. These results show that peptide proteinase inhibitors can be effective antimalarial compounds in vivo and suggest that the P. falciparum cysteine proteinase is a promising target for chemotherapy.
A Rate Adaptive Shaper for Differentiated Services (2000)

This memo describes several Rate Adaptive Shapers (RAS) that can be used in combination with the single rate Three Color Markers (srTCM) and the two rate Three Color Marker (trTCM) described in RFC2697 and RFC2698, respectively. These RAS improve the performance of TCP when a TCM is used at the ingress of a diffserv network by reducing the burstiness of the traffic. With TCP traffic, this reduction of the burstiness is accompanied by a reduction of the number of marked packets and by an improved TCP goodput. The proposed RAS can be used at the ingress of Diffserv networks providing the Assured Forwarding Per Hop Behavior (AF PHB). They are especially useful when a TCM is used to mark traffic composed of a small number of TCP connections.
Progressive Esophagitis from Acyclovir-Resistant Herpes Simplex (1989)

Clinically acquired acyclovir resistance in herpes simplex has usually been associated with a deficiency in viral thymidine kinase, which, in turn, has been linked with attenuated virulence in animal models. Diminished pathogenicity in thymidine kinase-deficient isolates has been partly responsible for controversies about the clinical significance of antiviral resistance. We report on a series of resistant virus isolates from a patient who had severe, progressive esophagitis. These isolates had various thymidine kinase activities, ranging from 2.8% to 130% when compared with the activity of the isolate obtained before treatment; the resistant isolate 615 retained enzyme activity as well as neurovirulence in an encephalitis model. Plaque purification showed a heterogeneous mixture containing at least one acyclovir-resistant, foscarnet-resistant plaque isolate (615.8) fully able to phosphorylate acyclovir. The 3.3-kbp BamHI fragment containing most of the DNA polymerase gene from isolate 615.8 was purified and used to successfully transfer both acyclovir and foscarnet resistance. Acquisition of in-vitro acyclovir resistance was associated with progression of clinical disease, as well as with maintenance of pathogenicity in an animal model and at least one mutation in viral DNA polymerase. Patients with herpes simplex infections that progress during acyclovir therapy should be observed for acquisition of resistance in the setting of antiviral chemotherapy; future studies should also consider the presence of heterogeneous virus populations in such patients.
The Spearman Estimator for Serial Dilution Assays (1961)

To estimate the density of a specific organism in a suspension, a common method is to form a series of dilutions of the original suspension. Then from each dilution a specified volume, hereafter referred to as a dose, is placed in each of several tubes. Later the tubes are examined for evidence of growth of the organism. Suppose k + 1 dilutions are used with concentrations of zi = a-'zoI i = 0, + 1, +2, * , + k. z0 is the highest concentration of original suspension used and a > 1 is the dilution factor. The following notation will be used:
Interleukin-22: Immunobiology and Pathology (2015)

Interleukin-22 (IL-22) is a recently described IL-10 family cytokine that is produced by T helper (Th) 17 cells, γδ T cells, NKT cells, and newly described innate lymphoid cells (ILCs). Knowledge of IL-22 biology has evolved rapidly since its discovery in 2000, and a role for IL-22 has been identified in numerous tissues, including the intestines, lung, liver, kidney, thymus, pancreas, and skin. IL-22 primarily targets nonhematopoietic epithelial and stromal cells, where it can promote proliferation and play a role in tissue regeneration. In addition, IL-22 regulates host defense at barrier surfaces. However, IL-22 has also been linked to several conditions involving inflammatory tissue pathology. In this review, we assess the current understanding of this cytokine, including its physiologic and pathologic effects on epithelial cell function.