gebhart/patrepeval huggingface dataset:
The complement C5 inhibitor crovalimab in paroxysmal nocturnal hemoglobinuria (2020)

Abstract Complement C5 inhibition is the standard of care (SoC) for patients with paroxysmal nocturnal hemoglobinuria (PNH) with significant clinical symptoms. Constant and complete suppression of the terminal complement pathway and the high serum concentration of C5 pose challenges to drug development that result in IV-only treatment options. Crovalimab, a sequential monoclonal antibody recycling technology antibody was engineered for extended self-administered subcutaneous dosing of small volumes in diseases amenable for C5 inhibition. A 3-part open-label adaptive phase 1/2 trial was conducted to assess safety, pharmacokinetics, pharmacodynamics, and exploratory efficacy in healthy volunteers (part 1), as well as in complement blockade–naive (part 2) and C5 inhibitor–treated (part 3) PNH patients. Twenty-nine patients were included in part 2 (n = 10) and part 3 (n = 19). Crovalimab concentrations exceeded the prespecified 100-µg/mL level and resulted in complete and sustained terminal complement pathway inhibition in treatment-naive and C5 inhibitor–pretreated PNH patients. Hemolytic activity and free C5 levels were suppressed below clinically relevant thresholds (liposome assay &amp;lt;10 U/mL and &amp;lt;50 ng/mL, respectively). Safety was consistent with the known profile of C5 inhibition. As expected, formation of drug-target-drug complexes was observed in all 19 patients switching to crovalimab, manifesting as transient mild or moderate vasculitic skin reactions in 2 of 19 participants. Both events resolved under continued treatment with crovalimab. Subcutaneous crovalimab (680 mg; 4 mL), administered once every 4 weeks, provides complete and sustained terminal complement pathway inhibition in patients with PNH, warranting further clinical development (ClinicalTrials.gov identifier, NCT03157635).
Human ϵ‐sarcoglycan is highly related to α‐sarcoglycan (adhalin), the limb girdle muscular dystrophy 2D gene1 (1998)

The dystrophin-glycoprotein complex (DGC) is critical for muscle membrane stability. The sarcoglycans are transmembrane proteins within the DGC, and the function of the sarcoglycans is unknown. Mutations in sarcoglycan genes cause autosomal recessive muscular dystrophy. We have identified a new sarcoglycan gene with high homology to alpha-sarcoglycan highlighting the redundancy of the DGC. This gene, named epsilon-sarcoglycan, has an identical intron-exon structure to alpha-sarcoglycan, and is more broadly expressed. The characterization of epsilon-sarcoglycan should make it possible to determine if it, like the other sarcoglycan genes, is mutated in muscular dystrophy.
100 /spl mu/J and 5.5 W Yb-fiber femtosecond chirped pulse amplifier system (2000)

Summary form only given. We have demonstrated the first all-fiber high-energy/power coherent pulse amplifier system based on Yb-doped fibers. Microjoule femtosecond pulses have been obtained at MHz-repetition rates. Achieved pulse durations and output powers constitute a significant improvement over the corresponding characteristics of Er-doped fiber amplifiers.
Effect of Hypoxia on Serum Iron and the Unsaturated Iron-Binding Capacity of Serum in Rats (1957)

In rats exposed to acute hypoxia there was immediate increase in unbound iron binding capacity (mainly siderophilin or transferrin) and fall in serum iron before the mor phology of the circulating blood was altered.
Mechanisms for Programmed Cell Death in the Nervous System of a Moth (2007)

In the moth Manduca sexta 50% of the abdominal motor neurons and interneurons die during the first days after the adult emerges. Although the dying motor neurons innervate larval muscles that also die at this time, the death of the neurons has been shown to be a direct response to an endocrine signal, the decline in ecdysteroids that occurs at the end of metamorphosis. The response to the withdrawal of the hormone apparently requires new synthesis of RNA and protein, as actinomycin-D and cycloheximide can prevent neuronal death. This selective neuronal death probably results from changes in gene activation. The fixed spatial and temporal pattern of neuronal death, however, suggests that trophic interactions among neurons may also be involved. Current work is focused on the fate of a pair of motor neurons, the MN-12 cells, in the third abdominal ganglion. Isolation of this ganglion from the thoracic ganglia can prevent the death of these cells at the time when they would normally die in response to removal of ecdysteroids. The factors mediating this effect may act in concert with the ecdysteroid decline to specify the exact time of death for individual neurons.
Dose and Wavelength of Laser Light Have Influence on the Repair of Cutaneous Wounds (2004)

Group IV (lambda 830 nm and lambda 685 nm, 20 J/cm(2)) presented better results at the end of the experimental period. It is concluded that low-level light therapy (LLLT) can have a positive biomodulatory effect on the repair of cutaneous wounds.
Gaussian profile estimation in two dimensions (2008)

We extend recent results for estimating the parameters of a one-dimensional Gaussian profile to two-dimensional profiles, deriving the exact covariance matrix of the estimated parameters. While the exact form is easy to compute, we provide a set of close approximations that allow the covariance to take on a simple analytic form. This not only provides new insight into the behavior of the estimation parameters, but also lays a foundation for clarifying previously published work. We also show how to calculate the parameter variances for the case of truncated sampling, where the profile lies near the edge of the array detector. Finally, we calculate expressions for the bias in the classical formulation of the problem and provide an approach for its removal. This allows us to show how the bias affects the problem of choosing an optimal pixel size for minimizing parameter variances.
Inference and effects of barcode multiplets in droplet-based single-cell assays (2020)

A widespread assumption for single-cell analyses specifies that one cell's nucleic acids are predominantly captured by one oligonucleotide barcode. Here, we show that ~13-21% of cell barcodes from the 10x Chromium scATAC-seq assay may have been derived from a droplet with more than one oligonucleotide sequence, which we call "barcode multiplets". We demonstrate that barcode multiplets can be derived from at least two different sources. First, we confirm that approximately 4% of droplets from the 10x platform may contain multiple beads. Additionally, we find that approximately 5% of beads may contain detectable levels of multiple oligonucleotide barcodes. We show that this artifact can confound single-cell analyses, including the interpretation of clonal diversity and proliferation of intra-tumor lymphocytes. Overall, our work provides a conceptual and computational framework to identify and assess the impacts of barcode multiplets in single-cell data.
Trace Element Reference Values in Serum Determined by Inductively Coupled Plasma Atomic Emission Spectrometry (2000)

Serum reference values for Ba, B, Cd, Cu, Fe, Mn, Li, Se, Sr, and Zn in 141 healthy Norwegians were determined. The trace element concentrations were determined by the inductively coupled plasma atomic emission spectrometry technique that we have recently validated. The reference intervals were established according to the recommendations of the International Federation of Clinical Chemistry and Laboratory Medicine. Also coverage intervals with coverage uncertainties were calculated according to the International Union of Pure and Applied Chemistry. The population studied consisted of 69 men and 72 women of the ages 21-87 years. The effects of gender, age, smoking, and oral contraceptives on serum levels of trace elements were investigated. Median concentrations of the different trace elements in (micromol/l) were as follows: Ba (0.44), B (1.50), Cd (0.004), Cu (17.1), Fe (21.4), Li (0.06), Mn (0.003), Se (1.26), Sr (0.17), and Zn (13.3). An increase in serum Ba and Sr was detected with age. These metals and Se were also significantly higher in women over 50 years of age in comparison to younger women. Women had higher serum Cu than men and those on oral contraceptives had higher serum Cu and Fe. Serum B tended to increase with age, while it was significantly reduced with smoking.
Deep Sliding Shapes for Amodal 3D Object Detection in RGB-D Images (2016)

We focus on the task of amodal 3D object detection in RGB-D images, which aims to produce a 3D bounding box of an object in metric form at its full extent. We introduce Deep Sliding Shapes, a 3D ConvNet formulation that takes a 3D volumetric scene from a RGB-D image as input and outputs 3D object bounding boxes. In our approach, we propose the first 3D Region Proposal Network (RPN) to learn objectness from geometric shapes and the first joint Object Recognition Network (ORN) to extract geometric features in 3D and color features in 2D. In particular, we handle objects of various sizes by training an amodal RPN at two different scales and an ORN to regress 3D bounding boxes. Experiments show that our algorithm outperforms the state-of-the-art by 13.8 in mAP and is 200× faster than the original Sliding Shapes.
FLUOROGENIC SUBSTRATES FOR β-D-GALACTOSIDASES AND PHOSPHATASES DERIVED FROM FLUORESCEIN (3, 6-DIHYDROXYFLUORAN) AND ITS MONOMETHYL ETHER (1963)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
Role of the Pruritic Cytokine IL-31 in Autoimmune Skin Diseases (2019)

Many autoimmune skin diseases, such as bullous pemphigoid (BP), psoriasis and certain types of chronic urticaria, are associated with intensive pruritus. While histamine and neuropeptides have previously been ascribed to play a role in itch that accompanies these diseases, recent evidence suggests that the pruritogenic cytokine interleukin (IL)-31 is a major driver of pruritic responses. IL-31 was originally shown to be produced by activated helper T cells, particularly Th2 cells, mast cells, macrophages and dendritic cells. However, more recent evidence demonstrated that eosinophils are a major source of this cytokine too, particularly in bullous pemphigoid. Basophils have also been shown to express the cytokine which, through autocrine action, strongly supports the production of other Th2-type cytokines from these cells. These investigations suggest that the dynamic recruitment of eosinophils and basophils in some autoimmune skin diseases could play an important role in the severity of IL-31-mediated itch. Furthermore, these studies suggest that IL-31, in addition to its pruritic actions, also has potential immunomodulatory roles in terms of supporting Th2-type immunity, which often underpins IgE-associated autoimmune diseases (such as bullous pemphigoid and urticaria) as well as allergies. While the role of IL-31 in psoriasis remains to be clarified, current evidence shows that this cytokine plays a major role in BP, chronic spontaneous urticaria and dermatomyositis. This suggests potential use of IL-31 receptor-blocking therapeutic approaches (e.g., Nemolizumab) for the treatment of IL-31-associated disorders.
A cDNA-dependent scintillation proximity assay for quantifying apolipoprotein A-I (1997)

We have developed a cDNA-dependent scintillation proximity assay (SPA) for rabbit apolipoprotein A-I that follows a classic radioimmunoassay scheme, in that antiserum and radiolabeled ligand are used in a process to quantify a source containing unlabeled ligand. To synthesize radiolabeled ligand we isolated a full-length rabbit apolipoprotein A-I (apoA-I) cDNA, transcribed the corresponding RNA in vitro, and synthesized radiolabeled apoA-I by including tritiated leucine in an in vitro translation reaction. Assay conditions were established which allowed quantification of unlabeled apoA-I over a range of 0.2 to 4 nanograms with intra- and interassay coefficients of variation of 5% and 10%, respectively. Purified rabbit apoA-I, apoA-I in rabbit liver parenchymal cell conditioned media, and apoA-I contained in rabbit plasma all generated parallel titration curves. Quantification of rabbit plasma apoA-I was not affected when sheep anti-rabbit apoA-I serum was mixed with sheep anti-rabbit apoB or apoE serum; thus, the antibody need not be specific to quantify the ligand of interest. To show utility of the assay, apoA-I mass was quantified in in vitro and in vivo models displaying altered apoA-I levels. In each model apoA-I values from the cDNA-dependent SPA and the established methodologies of Western blotting and electroimmunodiffusion were highly correlated. The approach outlined in this report should permit rapid development of scintillation proximity assays for other proteins given the widespread availability of full-length cDNAs.
Growth-inhibitory Effects of Diphenylhydantoin on Human Brain Tumor Cells in Culture (1978)

Diphenylhydantoin (DPH, phenytoin sodium, Dilantin) inhibited the growth of cultured human astrocytoma cells in 7 of the 10 cell lines studied. This inhibition, determined by a microtiter assay, was dose-dependent; DPH levels of 20 micrograms/ml and above produced significant depression of growth in astrocytoma cultured cells. However, normal cultured human astrocytes were not affected until DPH levels of 60 micrograms/ml and above were added to the cells; normal fibroblasts also showed no growth inhibition up to 100 micrograms/ml. We have confirmed that DPH is 1.5 times as concentrated in tumor tissue as it is in normal tissue and serum. These findings suggest that DPH has properties that inhibit the growth of human astrocytoma cells in tissue culture at levels that are achievable clinically.
Evidence of Association between Smoking and α7 Nicotinic Receptor Subunit Gene in Schizophrenia Patients (2004)

A number of studies have suggested that the alpha-7-nicotinic receptor D15S1360 polymorphism is associated with schizophrenia and a deficiency in the normal inhibition of the P50 auditory-evoked response. Schizophrenia patients and some of their unaffected relatives show a failure of inhibition in their 50-ms response to the second of a pair of tones. Biochemical studies have suggested that the alpha7 nicotinic acetylcholine receptor is involved in this sensory gating deficit. Furthermore, high-dose nicotine transiently normalizes the abnormality in P50 inhibition in schizophrenic patients and in their relatives. Schizophrenic patients are unusually heavy smokers, and up to 85% of hospitalized schizophrenic patients smoke. This rate is three times higher than the general population, and may represent an attempt to self-medicate through this pathophysiologic mechanism. Despite schizophrenics' extremely heavy nicotine use, nicotinic receptor genes have not been previously investigated in relation to smoking in schizophrenia. In this study, we hypothesized that the D15S1360 marker is associated with smoking in patients with schizophrenia. We found an association between the homozygous 113 bp allele and smoking risk (chi2=10.37, 3 df, p=0.015). Although this novel finding requires replication, it suggests that further study into the relationship between schizophrenia and nicotine system genes is warranted.
A small interfering RNA targeting proteinase‐activated receptor‐2 is effective in suppression of tumor growth in a Panc1 xenograft model (2007)

Proteinase-activated receptor-2 (PAR-2), which is a G protein-coupled receptor, is activated in inflammatory processes and cell proliferation. We previously demonstrated that an anti-PAR-2 antibody suppresses proliferation of human pancreatic cells in vitro. However, there have been no studies of PAR-2 signaling pathways in vivo. The aim of this study was to determine whether blockade of PAR-2 by RNA interference influences pancreatic tumor growth. We originally constructed small interfering RNAs (siRNAs) targeting human PAR-2, and performed cell proliferation assays of Panc1 human pancreatic cancer cell line with these siRNAs. Intratumoral treatment with these PAR-2 siRNAs and atelocollagen was also performed in a xenograft model with nude mice and Panc1 cells. siRNAs against human PAR-2 inhibited proliferation of Panc1 cells, whereas control scramble siRNAs had no effect on proliferation. The PAR-2 siRNAs dramatically suppressed tumor growth in the xenograft model. PAR-2-specific siRNA inhibited growth of human pancreatic cancer cells both in vitro and in vivo. Blockade of PAR-2 signaling by siRNA may be a novel strategy to treat pancreatic cancer.
Bacteria Expressing Avirulence Gene D Produce a Specific Elicitor of the Soybean Hypersensitive Reaction (1990)

Production of the avrD elicitor by P. s. pv. glycinea cells carrying the cloned avrD gene occurred independently of the hrp genes, considered important for pathogenicity and HR induction by certain P. syringae pathovars. The results indicated that expression of avirulence gene D in P. syringae pathovars and in E. coli causes them to produce a diffusible, elicitor-active molecule which initiates cultivar-specific induction of the HR
A method for testing development (1987)

Hans-Jorgen Marker. Une méthode d'analyse de séries temporelles lacunaires. Il arrive que l'on dispose d'observations numériques en nombre insuffisant pour utiliser les méthodes de calcul traditionnelles. A partir de séries lacunaires concernant des manoirs danois du XVIIe siècle, l'auteur propose et teste une méthode fondée sur la régression logarithmique dans une distribution normale et la confronte à une hypothèse historique.
Localization of the site of the murine IgG1 molecule that is involved in binding to the murine intestinal Fc receptor (1994)

Site-directed mutagenesis of a recombinant Fc hinge fragment has recently been used to localize the site of the murine IgG1 molecule that is involved in the control of catabolism (the "catabolic site"). In the current study, the effects of these CH2 and CH3 domain mutations (Ile 253 to Ala 253, His 310 to Ala 310, Gln 311 to Asn 311, His 433 to Ala 433 and Asn 434 to Gln 434) on intestinal transfer of Fc hinge fragments in neonatal mice have been analyzed. Studies using direct transfer and competition assays demonstrate that the mutations affect the transmission from intestinal lumen into serum in a way that correlates closely with the effects of the mutations on pharmacokinetics. Binding studies of several of the Fc hinge fragments to isolated neonatal brush borders have been used to confirm the in vivo transmission data. These analyses have resulted in the localization of the binding site for the intestinal transfer receptor, FcRn, to specific residues of the murine Fc hinge fragment. These residues are located at the CH2-CH3 domain interface and overlap with both the catabolic site and staphylococcal protein A (SpA) binding site. The pH dependence of IgG1 or Fc fragment binding to FcRn is consistent with the localization of the FcRn interaction site to a region of the Fc that encompasses two histidine residues (His 310 and His 433). To assess whether one or two FcRn binding sites per Fc hinge are required for intestinal transfer, a hybrid Fc hinge fragment comprising a heterodimer of one Fc hinge with the wild-type IgG1 sequence and a mutant Fc hinge with a defective catabolic site (mutated at His 310, Gln 311, His 433 and Asn 434) has been analyzed in direct and competition transmission assays. The studies demonstrate that the Fc hybrid is transferred with significantly reduced efficiency compared to the wild type Fc hinge homodimer and indicate that the binding to FcRn, and possibly subsequent transfer, is enhanced by the presence of two FcRn binding sites per Fc hinge fragment.
From Multifunctionalized Poly(ethylene imine)s toward Antimicrobial Coatings (2007)

Primary amine groups of branched poly(ethylene imine) (PEI) were functionalized with quaternary ammonium groups, alkyl chains of different length, allylic and benzylic groups in a one-step reaction, using a carbonate coupler. The structure of the obtained amphiphilic polymers was determined by means of 1H and 13C NMR spectroscopy. Depending on their hydrophilic/hydrophobic balance, the obtained polymers can be used as water-soluble disinfectants and for antimicrobial coating materials. The bactericidal properties of some of the amphiphilic polymers against Gram-negative and Gram-positive bacteria were investigated. Minimal inhibitory concentrations (log 4 reduction of bacterial growth) against Escherichia coli and Bacillus subtilis were determined in the range of 0.3-0.4 mg/mL and 0.03-0.04 mg/mL for water-soluble polymers. Glass slides coated with functionalized PEIs showed a reduction of colony forming units of at least 95%, at best 99.9%, against E. coli and B. subtilis.
Increased expression of two cDNAs encoding metallothionein‐like proteins during growth of Cicer arietinum epicotyls (1998)

The present study was undertaken to identify and characterize clones whose expression increase during Cicer arietinum epicotyl growth. Two cDNAs encoding two different plant metallothionein (MT)‐like proteins have been isolated from a cDNA library from epicotyls of Cicer arietinum L. cv. Castellana. The CanMT‐1 deduced protein appears to have the typical structure of type 1 MT where all Cys residues are in Cys‐X‐Cys motifs, while the CanMT‐2 has the typical structure of type 2 MT having Cys‐Cys and Cys‐X‐X‐Cys motifs within the N‐terminal domain. Both chickpea CanMTs are up‐regulated during epicotyl growth, showing increased expression in mature tissues, mostly CanMT‐1, which is undetectable in young epicotyls. Accordingly, stem of chickpea plants displayed the highest level of CanMT‐1 expression in the basal internode, with reduced growth, decreasing towards the apex. Osmotic stress by PEG, which inhibited growth, and ABA treatment induced the expression of MT‐like genes, which points to a relationship between chickpea MTs and ABA‐mediated stress response. Unlike CanMT‐2, CanMT‐1 is induced in chickpea epicotyls by cadmium indicating a different function for both clones. We conclude that these MT‐like proteins, in particular CanMT‐1, are regulated by the developmental stage and may participate in cell maturation process.
A survey of the CP/M software market (1979)

Personal computing is not as new a field as the public relations staff at Radio Shack would have us believe. In the good old days (before OS), programmers often had dedicated use of even the largest machines. In 1966, Fred Gruenberger wrote and article entitled "Are Small, Free-Standing Computers Here to Stay?" which appeared in Datamation. His conclusion was that they were here to stay and that they would also be used as time sharing terminals part of the time. In 1967, Tom Steel wrote an SDC internal note which not only predicted that small computers were here to stay, but that the average person might be able to afford to own one. His prediction was for a $25,000 personal computer with the power of a 7090 by the mid 1970s and a market size of 5--20 million units.
Gene expression profiles derived from fine needle aspiration correlate with response to systemic chemotherapy in breast cancer (2002)

This study supports the suitability of FNA-derived cDNA microarray expression profiling of breast cancers as a comprehensive genomic approach for studying the mechanisms of drug resistance. Our findings also demonstrate the potential of monitoring post-chemotherapy changes in expression profiles as a measure of pharmacodynamic effect and suggests that these approaches might yield useful results when validated by larger studies.