gebhart/patrepeval huggingface dataset:
Darbepoetin alfa. Amgen. (2001)

Amgen has launched darbepoetin alfa, synthetic recombinant novel erythropoiesis stimulating protein (NESP), for the treatment of anemia associated with renal disease. The drug was approved by the European Commission in June 2001, under the tradename Aranesp, for the treatment of anemia in chronic kidney failure including patients on and not yet on dialysis. The company launched the drug on day one of its approval in the following countries: Germany, Sweden, Denmark, Portugal, the Netherlands, the UK and Austria. Roll out of the drug in Italy, Greece and France will follow as soon as pricing and reimbursement issues are resolved [412240], [412357]. By January 2001, the product was still under review and the company anticipated approval during the first half of 2001 in both the US and Europe [396802]. Launch in the US had originally been scheduled for 2000 [387293], [396802] and Japanese launch is planned for 2004 or 2005 [405915]. In January 2001, Amgen reported that the first pivotal trial of darbepoetin alfa in treating oncology patients with anemia was successful [396526], [396802]. The company anticipated a phase III trial in US patients in 2001 for the oncology indication 13977941. In the fourth quarter of 2000, darbepoetin alfa entered phase I trials in Japan. Japanese development of darbepoetin alfa was being conducted by Kirin Brewery (under the research code KRN-321) [396653]. In January 2001, Genesis Pharma licensed the rights to distribute, market and sell darbepoetin alfa for the treatment of anemia, in Greece and Cyprus [396437]. MegaPharm Ltd signed an agreement with Amgen in February 2001, granting MegaPharm certain exclusive rights to distribute, market and sell darbepoetin alfa in Israel [398897]. In February 2000, Merrill Lynch predicted that darbepoetin alfa sales will be in excess of $1.4 billion at maturity [355817]. In October 2000, darbepoetin alfa annual sales were predicted to hit $3 billion [387293].
Advanced nanostructures for the control of biofouling: The FP6 EU Integrated Project AMBIO (2008)

The colonization of man made structures by marine or freshwater organisms or “biofouling” is a problem for maritime and aquaculture industries. Increasing restrictions on the use of toxic coatings that prevent biofouling, create a gap in the market that requires new approaches to produce novel nonbiocidal alternatives. This review details the systematic strategy adopted by an FP6 EU Integrated Project “AMBIO” to develop fundamental understanding of key surface properties that influence settlement and adhesion of fouling organisms. By this approach the project contributes to the understanding of fundamental phenomena involved in biofouling, and to the development of environmentally benign solutions by coating manufacturers within the consortium. © 2008 American Vacuum Society.
The Condensation of Chromatin in Apoptotic Thymocytes Shows a Specific Structural Change (1997)

Chromatin condensation and DNA cleavage at internucleosomal sites have been recognized early as hallmarks of apoptosis, and it has been suggested that extensive DNA chain scission could directly result in the formation of dense chromatin bodies. Here we have shown that no causal relationship exists between DNA degradation and chromatin condensation in glucocorticoid-induced thymocyte apoptosis. The chromatin rearrangement occurred independent of as well as prior to DNA cleavage and involved a specific conformational change at the nucleosome level. In the early stages of the process, the core particles appeared to be tightly packed face-to-face in smooth 11-nm filaments that progressively folded to generate a closely woven network. The network finally collapsed, producing dense apoptotic bodies. Since trypsin digestion relaxed condensed chromatin and histone H4 underwent appreciable deacetylation in the apoptotic cell, we suggest that changes in the DNA-histone interactions represented a major modulating factor of condensation.
O’ Bone Graft Derivatives and Substitutes. (1994)

1) Introduction (Urist, O'Connor and Burwell) 2) History of Bone Grafting and Bone Substitutes (Burwall) 3) Burwell Theory on the Importance of bone marrow in bone grafting (Burwell) 4) Use of free vasclilarized bone grafts (Roulhalamin) 5) Open bone grafting in the treatment of infected non-unions (Papineau) 6) Massive bone allografts (Tomford and Mankin) 7) A perspective on bone banking in the US (Tomford) 8) Scientific and economic aspects of tissue banking (Phillips) 9) Use of decalbone in healing of osseous cystic lesions (Goel and Tuli) 10) Clinical use of pyrost (Katthagen and Mittelmeier) 1 1) Results of basic and clinical studies of true bone ceramics (Tamaki, Sakurai and Kawakami) 12) Bone bonding behaviour and clinical use of A-W glass ceramics (Yamamuro) 13) Development and clinical use of coral-derived hydroxyapatite graft substitutes (Bucholz) 14) Collagraft combined with autogeneic bone marrow: experimental and clinical results (Kocialkowski, Wallace and Burwall) 15) Biodegradable bone graft substitutes (Doyle) 16) A quantitative study of the donor and recipient contributions to osteogenesis in long-term experimental bone grafts.
Effects of Thymostimulin with Combination Chemotherapy in Patients with Aggressive Non-Hodgkinʼs Lymphoma (1995)

The purpose of this study was to test the efficacy and safety of thymostimulin (TS) administered in addition to conventional chemotherapy in patients with intermediate- and high-grade non-Hodgkin's lymphoma (IG, HG-NHL). A total of 150 patients with newly diagnosed IG- or HG-NHL were entered in a multicenter trial to compare the effectiveness of two different third-generation regimens (MACOP-B versus ProMACE-CytaBOM) and were randomized to receive chemotherapy (CT) alone or CT + TS. In both regimens doxorubicin was replaced by a 20% higher dose of epidoxorubicin. TS was administered i.m. at a dose of 1 mg/kg daily on days 22-28 of each drug course to patients treated with ProMACE-CytaBOM, and on days 22-29, 50-57, and 77-85 to patients treated with MACOP-B. There were 134 fully evaluable patients: 68 treated with CT alone and 66 treated with CT + TS. Patients treated with CT + TS had a higher complete remission (CR) rate compared to patients given CT alone (59.1% vs 42.4%; P = .05). CR were significantly higher for patients treated with CT + TS in the groups with IG-NHL (P = .01), in those aged less than 60 years (P = .05), with good performance status (P = .05), and normal hemoglobin levels (P = .05). Four-year survival rates are 64.5% for patients treated with CT + TS and 43.0% for those treated with CT alone (P = .30). No difference between the two treatment arms have been observed as regards drug-related toxicity and the number and severity of infectious episodes. The use of TS during the 7 days before chemotherapy has been associated with a significantly superior CR rate. The advantage of CT + TS was mostly obtained in patients with IG-NHL, and those with good performance status or normal hemoglobin levels. In these patients TS may have potentiated the host reactions against the tumor, leading to an increase in NK activity and the production of cytokines. This postulated increase in the effectiveness of chemotherapy after TS might also explain the absence of the expected myeloprotective action.
The Bicyclo[1.1.1]pentane Framework—an Excellent Relay for π/σ Conjugation (1990)

Photoelectron spectra of the bicyclo[1.1.1]pentanes 1 and 2 reveal a high degree of splitting (0.7 eV) between the π-MOs of the ethynyl residues and the 4p orbitals of the bromine atoms, respectively. This is presumably due to strong interaction between the π systems and the σ system of the bicyclopentane framework. A similarly strong interaction has been demonstrated between the π and σ systems in 3. These observations are of considerable interest from the standpoint of the bicyclo[1.1.1]pentyl moiety serving as a potential subunit in the construction of oligomers and for promoting energy transfer over long molecular distances.
Pathogenesis of Mammary Carcinomas Induced in Rats by 7, 12-Dimethylbenz[a]anthracene2 (1977)

The pathogenesis of mammary carcinomas was studied in Spragu-Dawley virgin female rats after gastric Instillation of 7,12-dimethylbenz[a]anthracene (DMBA) at 55 days of age. Nine rats were killed weekly, from the time of DMBA inoculation until the 15th week after treatment. All the glands of each animal were studied in both cleared wholemounts and paraffin sections. The earliest observed lesion was hyperplasia of the end-bud epithelium, which appeared as a multifocal phenomenon as early as 14 days post Inoculation. Intraductal proliferation of end buds evolved to intraductal carcinomas, which formed either cribriform or papillary patterns. Every carcinoma observed was ductal in origin. Differentiation of the alveolar portion of the gland led to adenomas, hyperplastic alveolar nodules, and cysts. The presence of the terminal end buds at the time of DMBA administration was considered to play an important role in the genesis of carcinomas.
The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging‐Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease (2011)

The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia.
Mechanisms of the pro- and anti-oxidant actions of nitric oxide in atherosclerosis (2000)

The association of nitric oxide (NO) with cardiovascular disease has long been recognized and the extensive research on this topic has revealed both pro- and anti-atherosclerotic effects. While these contradictory findings were initially perplexing recent studies offer molecular mechanisms for the integration of these data in the context of our current understanding of the biochemistry of NO. The essential findings are that the biochemical properties of NO allow its exploitation as both a cell signaling molecule, through its interaction with redox centers in heme proteins, and an extremely rapid reaction with other biologically relevant free radicals. The direct reaction of NO with free radicals can have either pro- or antioxidant effects. In the cell, antioxidant properties of NO can be greatly amplified by the activation of signal transduction pathways that lead to the increased synthesis of endogenous antioxidants or down regulate responses to pro-inflammatory stimuli. These findings will be discussed in the context of atherosclerosis.
IEC-6 Intestinal Cell Death Induced by Bovine Milk α-Lactalbumin (2005)

Potent inhibition of cell proliferation was found for commercial preparations of bovine alpha-lactalbumin on cultured intestinal cell line IEC-6 albeit lot-dependent. The inhibition was irreversible and a single exposure to the culture medium containing alpha-lactalbumin of an active lot for a period as short as 30 min was enough to provoke cell death, possibly through apoptosis. The oligomer fraction from size exclusion chromatography was significantly robust, while the monomer fraction remained totally inert, in inducing cell death. Incubation at 37 degrees C for 5 d with 30% trifluoroethanol in acetate, pH 5.5, in a slowly rotating test tube rendered the monomer fraction cytotoxic. Again, the resulting inhibitory activity was found in the oligomer fraction from size exclusion chromatography, with emergence of subtle peaks at 22- and 30-kDa. Furthermore, the occurrence of SDS-stable 30-kDa as well as 20-kDa bands on electrophoresis was a common feature for alpha-lactalbumin with the activity inducing cell death. Thus, a certain dimeric state can be implicated in the cytotoxicity of bovine alpha-lactalbumin.
Reversal of Senescence in Mouse Fibroblasts through Lentiviral Suppression of p53 (2003)

Senescence is generally defined as an irreversible state of G(1) cell cycle arrest in which cells are refractory to growth factor stimulation. In mouse embryo fibroblasts (MEFs), induction of senescence requires the presence of p19(ARF) and p53, as genetic ablation of either of these genes allows escape from senescence and leads to immortalization. We have developed a lentiviral vector that directs the synthesis of a p53-specific short hairpin transcript, which mediates stable suppression of p53 expression through RNA interference. We show that suppression of p53 expression in senescent MEFs leads to rapid cell cycle re-entry, is associated with loss of expression of senescence-associated genes, and leads to immortalization. These data indicate that senescence in MEFs is reversible and demonstrate that both initiation and maintenance of senescence is p53-dependent.
INTRA-ARTICULAR SURGERY FOR DEGENERATIVE ARTHRITIS OF THE KNEE (1967)

1. The technique of the intra-articular surgery employed by the late Mr K. H. Pridie for osteoarthritis of the knee is described. 2. The results of sixty-two operations in sixty patients are analysed. The results in forty-eight knees (77 per cent) were pleasing to the patient. Forty knees (64 per cent) were rated as good at review. 3. The operation is most suitable for relatively active healthy people whose disability warrants a comparatively painful operation and lengthy rehabilitation. 4. The operation was most successful for relieving pain and improving stability. Functional improvement was less. 5. Results were remarkably permanent. The knees showed little tendency towards further deterioration. 6. Most of the bad results were associated with removal of the patella. A possible technical reason for this has been discussed.
Association of genetic markers with some eye diseases. (1983)

In this study ocular conditions like cataract, corneal dystrophy, retinal detachment, primary glaucoma, myopia and strabismus have been examined for certain genetic markers to estimate the relative risks involved. The incidence of nontasters for PTC was significantly high in cases with congenital cataract, aphakic retinal detachment and convergent and divergent squint as compared to controls. Among nontasters, the frequency of total taste blindness was strikingly high in the disease group as compared to controls. Blood group A individuals showed significantly high risk for zonular cataract, corneal dystrophy and convergent squint; group B individuals for zonular cataract and group O individuals for nuclear cataract, myopia and convergent squint. There was a high preponderance of non-secretors in zonular cataract and primary glaucoma cases when compared to controls. The incidence of HbS (one case with primary glaucoma and the other with granular corneal dystrophy) and HbD (one case with senile cataract) were considered as chance occurrences. A strong association was found between Hp 2-2 and retinal detachments specially those with vitreous degenerations. In general, when compared to controls, the frequency of Hp 2-2 was relatively low in nuclear, zonular, cortical and senile cataracts, while it was high in rest of the diseases.
PU-Net: Point Cloud Upsampling Network (2018)

Learning and analyzing 3D point clouds with deep networks is challenging due to the sparseness and irregularity of the data. In this paper, we present a data-driven point cloud upsampling technique. The key idea is to learn multi-level features per point and expand the point set via a multi-branch convolution unit implicitly in feature space. The expanded feature is then split to a multitude of features, which are then reconstructed to an upsampled point set. Our network is applied at a patch-level, with a joint loss function that encourages the upsampled points to remain on the underlying surface with a uniform distribution. We conduct various experiments using synthesis and scan data to evaluate our method and demonstrate its superiority over some baseline methods and an optimization-based method. Results show that our upsampled points have better uniformity and are located closer to the underlying surfaces.
Purification and characterization of an elastinolytic proteinase secreted by cercariae of Schistosoma mansoni. (1985)

An elastinolytic proteinase secreted by tissue-invasive larvae of Schistosoma mansoni has been purified to homogeneity. Size-exclusion chromatography and chromatofocusing were used to purify the enzyme 18-fold from crude larval secretions. The native enzyme has a molecular weight of 30,000, a pI of 8, a pH optimum of 9, and a calcium dependence of 2 mM. A second Mr 17,000 form of the enzyme was present in crude secretions and appears to be an autoproteolysis product. The enzyme is a serine proteinase that preferentially binds tetrapeptide inhibitors or substrates with an aromatic or hydrophobic residue at the P-1 site. In addition to being active against elastin, the enzyme degrades Azocoll, gelatin, laminin, fibronectin, keratin, and type IV collagen.
Anthrax Protective Antigen Delivered bySalmonella entericaSerovar Typhi Ty21a Protects Mice from a Lethal Anthrax Spore Challenge (2009)

Bacillus anthracis, the etiological agent of anthrax disease, is a proven weapon of bioterrorism. Currently, the only licensed vaccine against anthrax in the United States is AVA Biothrax, which, although efficacious, suffers from several limitations. This vaccine requires six injectable doses over 18 months to stimulate protective immunity, requires a cold chain for storage, and in many cases has been associated with adverse effects. In this study, we modified the B. anthracis protective antigen (PA) gene for optimal expression and stability, linked it to an inducible promoter for maximal expression in the host, and fused it to the secretion signal of the Escherichia coli alpha-hemolysin protein (HlyA) on a low-copy-number plasmid. This plasmid was introduced into the licensed typhoid vaccine strain, Salmonella enterica serovar Typhi strain Ty21a, and was found to be genetically stable. Immunization of mice with three vaccine doses elicited a strong PA-specific serum immunoglobulin G response with a geometric mean titer of 30,000 (range, 5,800 to 157,000) and lethal-toxin-neutralizing titers greater than 16,000. Vaccinated mice demonstrated 100% protection against a lethal intranasal challenge with aerosolized spores of B. anthracis 7702. The ultimate goal is a temperature-stable, safe, oral human vaccine against anthrax infection that can be self-administered in a few doses over a short period of time.
The kinetics of substrate-induced inactivation (1991)

The kinetics of a branched-pathway mechanism for a simple enzymic reaction were studied. In this mechanism there is reversible formation of an inactive form of the second complex along the pathway. This substrate-induced inactivation typically results in the progress curve showing a burst. Three parameters can be obtained from the progress curve: the initial rate, the final rate and the rate constant characterizing the transient. The rate constant for the conversion of the inactive form of the complex into the active form can be obtained either from these parameters or by measuring the regain of enzymic activity. The partition ratio can also be obtained from the three parameters; this is the ratio of the rate of conversion of complex into product to the rate of conversion of complex into inactive form. Simulations give guidance to the conditions required for accurate determinations of the rate constants.
Intra- and Interchain Disulfide Bridges of the Human J Chain in Secretory Immunoglobulin A (1992)

All intra J chain disulfide bridges of human sIgA, the disulfide bonds between the J chain and the two IgA monomers, and one inter IgA monomer disulfide bridge were determined. sIgA was isolated from colostrum of healthy women and digested with IgA1-specific protease followed by cyanogen bromide cleavage. This procedure generated fragments of 140 kDa, 60 kDa, and 28 kDa. The 28-kDa polypeptide comprised the complete J chain covalently bound to two alpha 1 chain octapeptides derived from the C-termini of two alpha 1 chains. The 28-kDa fragment was digested with trypsin. The resulting peptides were purified by RP-HPLC, and subsequently characterized by amino-acid analysis, mass spectrometry, and gas phase sequencing. These data unequivocally show that the J chain cysteines C1-C6, C4-C5, and C7-C8 form intra chain disulfide bridges. The second (C2) and the third (C3) J chain cysteines are disulfide linked to two alpha chain cysteines (C17) joining the two IgA monomers of sIgA tail to tail. The remaining two alpha chains of the two monomers are directly bound to each other via their ultimate cysteines (C17-C17). A new model for the J chain in sIgA is presented.
Kalinin: an epithelium-specific basement membrane adhesion molecule that is a component of anchoring filaments. (1991)

Basal keratinocytes attach to the underlying dermal stroma through an ultrastructurally unique and complex basement membrane zone. Electron-dense plaques along the basal surface plasma membrane, termed hemidesmosomes, appear to attach directly to the lamina densa of the basement membrane through fine strands, called anchoring filaments. The lamina densa is secured to the stroma through a complex of type VII collagen containing anchoring fibrils and anchoring plaques. We have identified what we believe is a novel antigen unique to this tissue region. The mAbs to this antigen localize to the anchoring filaments, just below the basal-dense plate of the hemidesmosomes. In cell culture, the antigen is deposited upon the culture substate by growing and migrating human keratinocytes. Addition of mAb to the cultures causes the cells to round and detach, but does not impair them metabolically. Skin fragments incubated with antibody extensively de-epithelialize. These findings strongly suggest that this antigen is intimately involved in attachment of keratinocytes to the basement membrane. This antigen was isolated from keratinocyte cultures by immunoaffinity chromatography. Two molecules are observed. The most intact species contains three nonidentical chains, 165, 155, and 140 kD linked by interchain disulfide bonds. The second and more abundant species contains the 165- and 140-kD chains, but the 155-kD chain has been proteolytically cleaved to 105 kD. Likewise, two rotary-shadowed images are observed. The larger of the two, presumably corresponding to the most intact form, appears as an asymmetric 107-nm-long rod, with a single globule at one end and two smaller globules at the other. The more abundant species, presumably the proteolytically cleaved form, lacks the distal small globule. We propose the name "kalinin" for this new molecule.