gebhart/patrepeval huggingface dataset:
Antibody–Drug Conjugates (ADCs) Derived from Interchain Cysteine Cross-Linking Demonstrate Improved Homogeneity and Other Pharmacological Properties over Conventional Heterogeneous ADCs (2015)

Conventional antibody-drug conjugates (ADCs) are heterogeneous mixtures of chemically distinct molecules that vary in both drugs/antibody (DAR) and conjugation sites. Suboptimal properties of heterogeneous ADCs have led to new site-specific conjugation methods for improving ADC homogeneity. Most site-specific methods require extensive antibody engineering to identify optimal conjugation sites and introduce unique functional groups for conjugation with appropriately modified linkers. Alternative nonrecombinant methods have emerged in which bifunctional linkers are utilized to cross-link antibody interchain cysteines and afford ADCs containing four drugs/antibody. Although these methods have been shown to improve ADC homogeneity and stability in vitro, their effect on the pharmacological properties of ADCs in vivo is unknown. In order to determine the relative impact of interchain cysteine cross-linking on the therapeutic window and other properties of ADCs in vivo, we synthesized a derivative of the known ADC payload, MC-MMAF, that contains a bifunctional dibromomaleimide (DBM) linker instead of a conventional maleimide (MC) linker. The DBM-MMAF derivative was conjugated to trastuzumab and a novel anti-CD98 antibody to afford ADCs containing predominantly four drugs/antibody. The pharmacological properties of the resulting cross-linked ADCs were compared with analogous heterogeneous ADCs derived from conventional linkers. The results demonstrate that DBM linkers can be applied directly to native antibodies, without antibody engineering, to yield highly homogeneous ADCs via cysteine cross-linking. The resulting ADCs demonstrate improved pharmacokinetics, superior efficacy, and reduced toxicity in vivo compared to analogous conventional heterogeneous ADCs.
Extreme ultraviolet spectroscopy of helium–hydrogen plasma (2003)

Extreme ultraviolet spectroscopy was recorded on microwave discharges of helium with 2% hydrogen. Novel emission lines were observed with energies of q . 13.6 eV, q = 1, 2, 3, 7, 9, 11, or q . 13.6 eV, q = 4, 6, 8 less 21.2 eV corresponding to inelastic scattering of these photons by helium atoms due to excitation of He (1s2) to He (1s12p1). The average hydrogen atom temperature was measured to be 180–210 eV versus ≈3 eV for pure hydrogen. The electron temperature Te for helium–hydrogen was 30 500 ± 5% K compared to 7400±5% K for pure helium. Known explanations for the novel series of spectral lines and extraordinary broadening were ruled out.
Is Orbital Angular Momentum (OAM) Based Radio Communication an Unexploited Area? (2011)

We compare the technique of using the orbital angular momentum (OAM) of radio waves for generating multiple channels in a radio communication scenario with traditional multiple-in-multiple-out (MIMO) communication methods. We demonstrate that, for certain array configurations in free space, traditional MIMO theory leads to eigen-modes identical to the OAM states. From this we conclude that communicating over the sub-channels given by OAM states is a subset of the solutions offered by MIMO, and therefore does not offer any additional gains in capacity.
Clock Mutants of Drosophila melanogaster (1971)

Three mutants have been isolated in which the normal 24-hour rhythm is drastically changed. One mutant is arrhythmic; another has a period of 19 hr; a third has a period of 28 hr. Both the eclosion rhythm of a population and the locomotor activity of individual flies are affected. All these mutations appear to involve the same functional gene on the X chromosome.
Improved algorithms and data structures for solving graph problems in external memory (2002)

Recently, the study of I/O-efficient algorithms has moved beyond fundamental problems of sorting and permuting and into wider areas such as computational geometry and graph algorithms. With this expansion has come a need for new algorithmic techniques and data structures. In this paper, we present I/O-efficient analogues of well-known data structures that we show to be useful for obtaining simpler and improved algorithms for several graph problems. Our results include improved algorithms for minimum spanning trees, breadth-first search, and single-source shortest paths. The descriptions of these algorithms are greatly simplified by their use of well-defined I/O-efficient data structures with good amortized performance bounds. We expect that I/O efficient data structures such as these will be a useful tool for the design-of I/O-efficient algorithms.
Oxide TFTs: A Progress Report (2016)

For flat‐panel‐display backplane applications, oxide‐TFT technology is the new kid on the block – recently conceived and in its early stages of commercialization. How is it going for oxide‐TFT technology as it attempts to match up with a‐Si:H and LTPS technology?
Revised Response Criteria for Malignant Lymphoma (2007)

We hope that these guidelines will be adopted widely by study groups, pharmaceutical and biotechnology companies, and regulatory agencies to facilitate the development of new and more effective therapies to improve the outcome of patients with lymphoma.
Regulation of inducible peroxide stress responses (2002)

Summary Bacteria adapt to the presence of reactive oxygen species (ROS) by increasing the expression of detoxification enzymes and protein and DNA repair functions. These responses are co‐ordinated by transcription factors that regulate target genes in response to ROS. We compare three classes of peroxide‐sensing regulators: OxyR, PerR and OhrR. In all three cases, peroxides effect changes in the redox status of cysteine residues, but the molecular details are distinct. OxyR is converted into a transcriptional activator by the formation of a disulphide bond between two reactive cysteine residues. PerR is a metalloprotein that functions as a peroxide‐ sensitive repressor. Oxidation is modulated by metal ion composition and may also involve disulphide bond formation. OhrR represses an organic peroxide resistance protein and mediates derepression in response to organic peroxides. Peroxide sensing in this system requires a single conserved cysteine, which is oxidized to form a cysteine–sulphenic acid derivative.
Narrow-linewidth stimulated Brillouin fiber laser and applications (1991)

A stimulated Brillouin fiber ring laser with a spectral width of 2 kHz and an intrinsic linewidth of less than 30 Hz has been demonstrated. Applications of such a laser include laser linewidth narrowing, microwave frequency generation, high-rate amplitude modulation, and optical inertial rotation sensing.
Stress-induced Inhibition of ERK1 and ERK2 by Direct Interaction with p38 MAP Kinase (2001)

We have identified a direct physical interaction between the stress signaling p38alpha MAP kinase and the mitogen-activated protein kinases ERK1 and ERK2 by affinity chromatography and coimmunoprecipitation studies. Phosphorylation and activation of p38alpha enhanced its interaction with ERK1/2, and this correlated with inhibition of ERK1/2 phosphotransferase activity. The loss of epidermal growth factor-induced activation and phosphorylation of ERK1/2 but not of their direct activator MEK1 in HeLa cells transfected with the p38alpha activator MKK6(E) indicated that activated p38alpha may sequester ERK1/2 and sterically block their phosphorylation by MEK1.
Superconducting qubit network with controllable nearest-neighbour coupling (2005)

We investigate the design and functionality of a network of loop-shaped charge qubits with switchable nearest-neighbour coupling. The qubit coupling is achieved by placing large Josephson junctions (JJs) at the intersections of the qubit loops and selectively applying bias currents. The network is scalable and makes it possible to perform a universal set of quantum gates. The coupling scheme allows gate operation at the charge degeneracy point of each qubit, and also applies to charge-phase qubits. Additional JJs included in the qubit loops for qubit readout can also be employed for qubit coupling.
Prenatal diagnosis of cystic fibrosis by trehalase enzyme assay in amniotic fluid (1985)

Amniocentesis and amniotic fluid trehalase enzyme assay were offered to 14 pregnant women at a 1 in 4 risk for a child with cystic fibrosis. Twelve of these pregnancies were screened at the 18th week of gestation; ten proceeded to term, seven following the finding of a normal trehalase activity and three despite the low enzyme level in amniotic fluid. In all ten cases prenatal diagnosis proved to be correct. In two cases with low enzyme activity parents opted for termination at the 19th week, and with PAS-Alcian Blue staining some slight histochemical lesions characteristic of cystic fibrosis were seen in the exocrine glands, including the pancreas and intestinal mucosa, of both fetuses. The total protein content in the meconium of these fetuses was significantly higher than in the controls. Results suggest that trehalase assay in the amniotic fluid is a potential prenatal test for cystic fibrosis and it appears that in fetuses with cystic fibrosis some histochemical and biochemical abnormalities can be observed as early as the 19th week of gestation. The role of ultrasound examination as an additional procedure for the prenatal diagnosis of cystic fibrosis is also discussed.
The First Single-Step Immobilization of a Calix-[4]-arene onto the Surface of Silica (2002)

A novel synthetic method for immobilizing calixarene macrocycles onto the surface of silica is reported that does not require calixarene synthetic derivatization with a flexible tether. In part because of the rigidity of the linkage between the calixarene and the silica resulting from this method, immobilized site densities in excess of 0.2 mmol/g are obtained, which are the highest values reported to date on a per gram of material basis for anchored calixarenes on silica. The immobilized calixarenes contain lipophilic cavities that can be accessed with gas physisorption experiments at cryogenic temperatures, as well as with neutral organic molecular guests at room temperature. The toluene adsorption isotherm from aqueous solution clearly demonstrates a saturation coverage that is commensurate with formation of a 1:1 stoichiometric complex between the immobilized host and guest. The reversibility of adsorption within this class of materials is demonstrated with phenol, which is shown to bind reversibly via thermal desorption spectroscopy.
A Validated Quantitative Assay to Detect Occult Micrometastases by Reverse Transcriptase-Polymerase Chain Reaction of Guanylyl Cyclase C in Patients with Colorectal Cancer (2006)

Quantifying GCC mRNA in tissues by RT-PCR employing external calibration standards is analytically robust and reproducible, with high clinicopathologic sensitivity and specificity. This validated assay is being applied to approximately 10,000 lymph nodes in a prospective trial to define the sensitivity of GCC qRT-PCR for staging patients with colorectal cancer.
Efficacy of Antibody to PNAG Against Keratitis Caused by Fungal Pathogens (2016)

Poly-N-acetyl glucosamine is produced by clinically important fungal ocular pathogens. Antibody to PNAG demonstrated protection against Aspergillus and Fusarium keratitis, requiring T cells producing IL-17 and IL-22. These findings indicate the potential to prevent or treat fungal infections by vaccines and immunotherapeutics to PNAG.
Treatment of Acute Focal Cerebral Ischemia with Concentrated Albumin (1981)

The object of the investigation was to study the effects of concentrated albumin upon the evolution of cerebral infarction. Twenty adult cats lightly anesthetized with ketamine hydrochloride underwent right middle cerebral artery (MCA) occlusion for 6 hours. Ten cats were not treated and 10 cats received concentrated (i.e., 25 g/100 ml) human serum albumin (5 ml/kg i.v.) at the time of MCA occlusion. The blood volume increased 30 to 40% in the cats receiving concentrated albumin. The hematocrit fell for 32 +/- 5% (SD) before occlusion to 23 +/- 6% at 2.5 hours after occlusion in treated cats, whereas the hematocrit in untreated cats remained stable at 35 +/- 5. Regional cerebral blood flow (rCBF) changes in the right sylvian region were similar in the untreated and treated groups. The mean rCBF before occlusion was 42 +/- 11 ml/100 g/minute in the untreated cats and 44 +/- 8 ml/100 g/minute in the treated cats. Untreated and treated cats had similar reductions of rCBF in the right sylvian region to less than or equal to 18 ml/100 g/minute at some point after occlusion. An index of erythrocyte flow and microcirculatory resistance was determined by measuring the transit of 99Tc-labeled erythrocytes in the right sylvian region. The erythrocyte transit time before occlusion was 10 +/- 2 seconds in the untreated group and 9 +/- 1 seconds in the treated group. After 6 hours, the erythrocyte transit was 19 +/- 3 seconds in the untreated group and 15 +/- 3 seconds in the treated group (p less than or equal to 0.1), suggesting that less microcirculatory impairment occurred in some treated cats. Electroencephalographic changes during the initial 3 hours of occlusion were less severe in the treated cats than in the untreated cats, suggesting that the collateral flow in the border zone of the MCA territory initially may have been improved by treatment. Impairment of carbon perfusion, ischemic edema, and neuronal alterations after 6 hours of occlusion were the same in both groups. Increased permeability of the blood-brain barrier to Evans blue dye, however, was more marked in the treated group. The findings of the study indicate that concentrated albumin does not substantially modify the evolution of cerebral infarction.
Synthesis and Functionalization of meso-Aryl-Substituted Corroles (2000)

The Rothemund condensation reaction of pyrrole and aldehydes is an extensively used route to meso-tetraarylporphyrins, but simple modifications of the reaction conditions allow the formation of different macrocycles other than the expected porphyrin. In the presence of an excess of pyrrole, this modified Rothemund approach leads to the synthesis of meso-triary-substituted corroles. This methodology allows the preparation of a wide range of substituted corroles starting from commercially available products. Higher yields have been obtained in the case of benzaldehydes bearing electron-withdrawing substituents, while the reaction fails in the presence of 2,6-disubstituted benzaldehydes. Although if not isolated, some experimental evidences indicate that the linear 5,10,15-triphenylbilane 4 is the precursor of the final corrole ring. Reaction of 5,10,15-triphenylcorrole 2 with an excess of NBS leads to the complete bromination of the macrocycle. Spectroscopic characterization seems to indicate the formation of the porphodimethene-like structure 5, where the macrocyclic aromatic conjugation is interrupted at the 10 position. Metalation of this compound with cobalt acetate and PPh3 affords the corresponding complex. The X-ray crystal structure of triphenylphosphine [2,3,7,8,12,13,17,18-octabromo-5,10,15-tris(4-nitrophenyl)corrolato]- cobalt(III) 8 confirms the ability of corrole ring to retain an almost planar conformation when fully substituted at the peripheral position.
Double discharges in unipolar-pulsed dielectric barrier discharge xenon excimer lamps (2003)

Excitation of dielectric barrier discharge xenon excimer lamps by unipolar short square pulses is studied in this paper. Two discharges with different polarity are excited by each voltage pulse (double discharge phenomenon). The primary discharge occurs at the top or at the rising flank of the applied unipolar square pulse, which is directly energized by the external circuit. The secondary discharge with the reversed polarity occurs at the falling flank or shortly after the falling flank end (zero external voltage) depending on the pulse width, which is energized by the energy stored by memory charges deposited by the primary discharge. Fast-speed ICCD imaging shows the primary discharge has a conic discharge appearance with a channel broadening on the anode side. This channel broadening increases with increasing the pulse top level. Only the anode-side surface discharge is observed in the primary discharge. The surface discharge on the cathode side which is present in bipolar sine voltage excitation is not observed. On the contrary, the secondary discharge has only the cathode-side surface discharge. The surface discharge on the anode side is not observed. The secondary discharge is much more diffuse than the primary discharge. Time-resolved emission measurement of double discharges show the secondary discharge emits more VUV xenon excimer radiation but less infrared (IR) xenon atomic emission than the primary discharge. It was found that the IR xenon atomic emission from the secondary discharge can be reduced by shortening the pulse width. The energy efficiency of unipolar-pulsed xenon excimer lamps (the overall energy efficiency of double discharges) is much higher than that obtained under bipolar sine wave excitation. The output VUV spectrum under unipolar pulse excitation is found to be identical to that under sine wave excitation and independent of injected electric power.
Studies in a tumor spectrum.I. Comparison of the action of methylbis(2-chloroethyl)amine and 3-bis(2-chloroethyl)aminomethyl-4-methoxymethyl-5-hydroxy-6-methylpyridine on the growth of a variety of mouse and rat tumors (1952)

A TUMOR SPECTRUM I . Comparison of the Action of MethyEbis(2-chloroethy1)amine and 3 -B is(2-ch loro et h y 1)am i no m e t hy 1-4 -met hoxy m e t h y 1-5-h y droxy-
Biochemical characterization of two isoforms of FLT4, a VEGF receptor-related tyrosine kinase. (1995)

The FLT4 gene encodes a tyrosine kinase receptor related to the two identified receptors for vascular endothelial growth factor (VEGF), FLT1 and FLK1/KDR. Two isoforms of FLT4, differing by their C-terminal ends, have been identified. The long form has 65 additional amino acid residues. We have shown that FLT4 is a highly glycosylated, relatively stable, cell surface associated kinase of approximately 180 kDa. In order to study the signal transduction molecules associated with the FLT4 pathway, and in the absence of a known ligand, we constructed two chimeric molecules (FF4S and FF4L) made of the extracellular region of the CSF1 receptor (Fms gene product) and of the transmembrane and intracellular regions of either form of FLT4. These two chimeric forms were expressed in Rat 2 transfectants. We assayed the ligand-induced capacity of the FF4 short and long forms to sustain growth of Rat 2 cells in semisolid medium. In a soft agar assay, only the long form was able to induce the growth of Rat 2 cells upon ligand treatment. The two forms of FLT4 therefore have different functional capacities. We looked for association and/or phosphorylation of phospholipase C gamma (PLC gamma) and phosphatidylinositol-3'-phosphate (PI3K), after stimulation of the FF4 molecules by CSF1. Finally, we have studied the expression of the Flt4 gene in mouse embryos and in the adult by in situ hybridization. Flt4 transcripts were found at day 12.5 post-coïtum and thereafter, including the adult mouse, predominantly in the pericardium, pleural membranes and in the lung.
Role of replication time in the control of tissue-specific gene expression. (1987)

Late-replicating chromatin in vertebrates is repressed. Housekeeping (constitutively active) genes always replicate early and are in the early-replicating R-bands. Tissue-specific genes are usually in the late-replicating G-bands and therein almost always replicate late. Within the G-bands, however, a tissue-specific gene does replicate early in those cell types that express that particular gene. While the condition of late replication may simply be coincident with gene repression, we review evidence suggesting that late replication may actively determine repression. As mammals utilize a developmental program to Lyonize (facultatively heterochromatinize) whole X chromosomes to a late-replicating and somatically heritable repressed state, similarly another program seems to Lyonize individual replicons. In frogs, all genes begin embryogenesis by replicating during a very short interval. As the developmental potency of embryonic cells becomes restricted, late-replicating DNA gradually appears. This addition to the repertoire of gene control--i.e., repression via Lyonization of individual replicons--seems to have evolved in vertebrates with G-bands being a manifestation of the mechanism.
Characterization of Salmonella enterica Derivatives Harboring Defined aroC and Salmonella Pathogenicity Island 2 Type III Secretion System ( ssaV ) Mutations by Immunization of Healthy Volunteers (2002)

The attenuation and immunogenicity of two novel Salmonella vaccine strains, Salmonella enterica serovar Typhi (Ty2 Delta aroC Delta ssaV, designated ZH9) and S. enterica serovar Typhimurium (TML Delta aroC Delta ssaV, designated WT05), were evaluated after their oral administration to volunteers as single escalating doses of 10(7), 10(8), or 10(9) CFU. ZH9 was well tolerated, not detected in blood, nor persistently excreted in stool. Six of nine volunteers elicited anti-serovar Typhi lipopolysaccharide (LPS) immunoglobulin A (IgA) antibody-secreting cell (ASC) responses, with three of three vaccinees receiving 10(8) and two of three receiving 10(9) CFU which elicited high-titer LPS-specific serum IgG. WT05 was also well tolerated with no diarrhea, although the administration of 10(8) and 10(9) CFU resulted in shedding in stools for up to 23 days. Only volunteers immunized with 10(9) CFU of WT05 mounted detectable serovar Typhimurium LPS-specific ASC responses and serum antibody responses were variable. These data indicate that mutations in type III secretion systems may provide a route to the development of live vaccines in humans and highlight significant differences in the potential use of serovars Typhimurium and Typhi.
Polymer gels that can recognize and recover molecules (1995)

The design and development of a polymer gel that can selectively absorb and release metal ions is investigated; the recovery of metal ions has a cooperative switching effect. A synthetic method for producing polymers that can thermodynamically memorize a conformation and selectively absorb a target molecule is proposed.
Controlling Bioprocesses with Inorganic Surfaces:  Layered Clay Hemostatic Agents (2007)

Layered clays are shown to have a wide range of blood-clotting properties that appear to be influenced by surface charge. The most active clay clotting agent is as effective as a commercial zeolite hemostatic material, but does not release heat, making it a promising alternative to the zeolite.