gebhart/patrepeval huggingface dataset:
The Human Gene Mutation Database: towards a comprehensive repository of inherited mutation data for medical research, genetic diagnosis and next-generation sequencing studies (2017)

The Human Gene Mutation Database (HGMD<sup>®</sup>) constitutes a comprehensive collection of published germline mutations in nuclear genes that underlie, or are closely associated with human inherited disease. At the time of writing (March 2017), the database contained in excess of 203,000 different gene lesions identified in over 8000 genes manually curated from over 2600 journals. With new mutation entries currently accumulating at a rate exceeding 17,000 per annum, HGMD represents de facto the central unified gene/disease-oriented repository of heritable mutations causing human genetic disease used worldwide by researchers, clinicians, diagnostic laboratories and genetic counsellors, and is an essential tool for the annotation of next-generation sequencing data. The public version of HGMD ( http://www.hgmd.org ) is freely available to registered users from academic institutions and non-profit organisations whilst the subscription version (HGMD Professional) is available to academic, clinical and commercial users under license via QIAGEN Inc.
Vascular zip codes in angiogenesis and metastasis (2004)

In vivo screening of phage-displayed peptide libraries has revealed extensive molecular differences in the blood vessels of individual normal tissues. Pathological lesions also put their signature on the vasculature; in tumours, both blood and lymphatic vessels differ from normal vessels. The changes that characterize tumour blood vessels include selective expression of certain integrins. Peptides isolated by in vivo phage display for homing to tumours have been shown to be useful in directing therapeutic agents to experimental tumours. The targeting can enhance the efficacy of the therapy while reducing side effects. Phage screening has also revealed lung-specific vascular markers that promote tumour metastasis to the lungs by mediating specific adherence of tumour cells to the lung vasculature. These phage-screening studies have revealed a previously unsuspected degree of vascular specialization and provide potentially useful guidance devices for targeted therapies.
Expression, Purification, and Reconstitution of Receptor for Pituitary Adenylate Cyclase-activating Polypeptide (1998)

Human pituitary adenylate cyclase-activating polypeptide (PACAP) receptor was expressed in Sf9 insect cells and Chinese hamster ovary (CHO) cells. The recombinant receptor in Sf9 cell membranes had low affinity for 125I-PACAP27 (Kd = 155.3 pM) and was insensitive to guanosine 5'-O-3-thiotriphosphate (GTPgammaS), whereas the receptor in CHO membranes had a high affinity (Kd = 44.4 pM) and was GTPgammaS sensitive. The receptor in Sf9 membranes was converted to a high affinity state (Kd = 20-40 pM) following solubilization with digitonin. A large quantity (2 mg from 8 liters of insect cells) of the purified PACAP receptors (Bmax = 23.9 nmol/mg of protein) were obtained in a digitonin-induced high affinity state (Kd = 17.3 pM) using biotinylated ligand affinity chromatography. The apparent molecular weight of the purified receptor (Mr = 48,000) was smaller than that of the receptor from CHO cells (Mr = 58,000) due to differences in asparagine-linked sugar chains. The purified receptor reverted to a low affinity state (Kd = 182.6 pM) upon reconstitution into lipid vesicles, however, the receptor reconstituted with Gs protein had a high affinity (Kd = 40.2 pM) and was GTPgammaS sensitive. [35S]GTPgammaS binding to the reconstituted Gs protein was enhanced by PACAP27 and PACAP38 (EC50 = 42.5 and 9.4 pM, respectively) but not by antagonist PACAP(6-38), indicating that the purified receptor was functionally active.
Development of a simple diagnostic method for the glaucoma using ocular Fundus pictures. (2005)

There are approximately 2 million people who have glaucoma. And about 90% of glaucoma patients have chronic type disease, and most of them do not notice of their disease. Finally they will lost their eyesight by this disease. Therefore, it is necessary to develop the auto diagnostic method for glaucoma. Our objective of this study is the development of the auto diagnostic system for the glaucoma by using fundus photograph. In our system, digitized fundus photograph is tested in personal computer, and the ratio of the area of optic disk and the area of optic disk cup (named C/D ratio) is calculated and evaluated automatically. And then this system can checkup subject condition for glaucoma. In this paper, we will discuss our auto diagnostic system for the glaucoma.
The underlying pathway structure of biochemical reaction networks (1998)

Bioinformatics is yielding extensive, and in some cases complete, genetic and biochemical information about individual cell types and cellular processes, providing the composition of living cells and the molecular structure of its components. These components together perform integrated cellular functions that now need to be analyzed. In particular, the functional definition of biochemical pathways and their role in the context of the whole cell is lacking. In this study, we show how the mass balance constraints that govern the function of biochemical reaction networks lead to the translation of this problem into the realm of linear algebra. The functional capabilities of biochemical reaction networks, and thus the choices that cells can make, are reflected in the null space of their stoichiometric matrix. The null space is spanned by a finite number of basis vectors. We present an algorithm for the synthesis of a set of basis vectors for spanning the null space of the stoichiometric matrix, in which these basis vectors represent the underlying biochemical pathways that are fundamental to the corresponding biochemical reaction network. In other words, all possible flux distributions achievable by a defined set of biochemical reactions are represented by a linear combination of these basis pathways. These basis pathways thus represent the underlying pathway structure of the defined biochemical reaction network. This development is significant from a fundamental and conceptual standpoint because it yields a holistic definition of biochemical pathways in contrast to definitions that have arisen from the historical development of our knowledge about biochemical processes. Additionally, this new conceptual framework will be important in defining, characterizing, and studying biochemical pathways from the rapidly growing information on cellular function.
In vivo delivery of antisense oligonucleotides in pH-sensitive liposomes inhibits lipopolysaccharide-induced production of tumor necrosis factor-alpha in rats. (2001)

Kupffer cells play an important role in the pathogenesis of liver diseases. During endotoxemia and alcohol-induced liver disease, tissue injury is preceded by an excessive release of cytokines by these macrophages. Tumor necrosis factor-alpha (TNF-alpha) is one of the key cytokines associated with liver injury. Pre-exposure of animals to TNF-alpha antibodies has been shown to prevent macrophage-mediated liver injury in experimental animals. In this article, we describe a method to encapsulate in pH-sensitive liposomes and to deliver an antisense phosphorothioate oligonucleotide (TJU-2755) against TNF-alpha. We describe the efficacy of this formulation in inhibiting endotoxin-mediated production of TNF-alpha. The liposomes prepared were stable for over 4 weeks at pH 7.4, but readily released their contents when exposed to an acidic environment below pH 6, similar to the pH that exists in early endosomes. Male Sprague-Dawley rats were administered (i.v.) liposome-encapsulated TJU-2755 (1-2 mg/kg body wt.). Empty liposomes served as controls. Forty-eight hours postinjection, the animals were administered a single dose of lipopolysaccharide (50 microg/kg body wt.) and were sacrificed 90 min later. The TNF-alpha produced by excised liver incubated ex vivo and the levels of plasma TNF-alpha were determined. After a single administration of liposome-encapsulated antisense TJU-2755, a 30% reduction in TNF-alpha produced by liver slices was observed. Two daily doses of the antisense oligonucleotide inhibited TNF-alpha production by 50%. This was associated with a 65 to 70% reduction in plasma levels of TNF-alpha, compared with controls. These results indicate that oligonucleotide TJU-2755 encapsulated in pH-sensitive liposomes can be used to effectively reduce endotoxin-mediated production of TNF-alpha in macrophages in vivo and thus may be of value in attenuating or preventing macrophage-mediated liver injury.
Salivary mucins inhibit antibacterial activity of the cathelicidin-derived LL-37 peptide but not the cationic steroid CSA-13 (2008)

Cationic antimicrobial peptides (CAPs) are the effector molecules of innate immunity, similar in potency to classic antibiotics that function in the first-line of defence against infectious agents. The purpose of this study was to investigate the effects of negatively charged mucins on the antibacterial activity of the positively charged cathelicidin LL-37 peptide, its synthetic analogue WLBU2 and the antimicrobial cationic steroid CSA-13. Mucin, DNA, F-actin and hCAP-18/LL-37 in saliva samples were evaluated by microscopy or immunoblotting. Bacterial killing assays and determination of MICs were used to determine bactericidal activity. Binding of rhodamine-B-labelled LL-37 peptide to mucin was fluorimetrically assessed. Microscopic evaluation of saliva after addition of rhodamine-B-labelled LL-37 showed localization similar to that observed after the addition of a specific mucin-binding lectin. Immunoblotting confirmed the presence of hCAP-18/LL-37 in saliva samples and LL-37 peptide bound to isolated submaxillary gland mucin-coated plates. Mucin/LL-37 binding was partially prevented by treatment of mucin with neuraminidase, indicating involvement of sialic acid moieties. Decreased LL-37 and WLBU2 antibacterial activity was observed in the presence of mucin or dialysed human saliva, whereas CSA-13 antibacterial activity was significantly resistant to inhibition by mucins. This study shows that the antibacterial LL-37 peptide and its synthetic analogue WLBU2 are inhibited by salivary mucin and that the cationic steroid CSA-13 retains most of its function in the presence of an equal amount of mucin or saliva.
Diversity and Stratification of Archaea in a Hypersaline Microbial Mat (2008)

The Guerrero Negro (GN) hypersaline microbial mats have become one focus for biogeochemical studies of stratified ecosystems. The GN mats are found beneath several of a series of ponds of increasing salinity that make up a solar saltern fed from Pacific Ocean water pumped from the Laguna Ojo de Liebre near GN, Baja California Sur, Mexico. Molecular surveys of the laminated photosynthetic microbial mat below the fourth pond in the series identified an enormous diversity of bacteria in the mat, but archaea have received little attention. To determine the bulk contribution of archaeal phylotypes to the pond 4 study site, we determined the phylogenetic distribution of archaeal rRNA gene sequences in PCR libraries based on nominally universal primers. The ratios of bacterial/archaeal/eukaryotic rRNA genes, 90%/9%/1%, suggest that the archaeal contribution to the metabolic activities of the mat may be significant. To explore the distribution of archaea in the mat, sequences derived using archaeon-specific PCR primers were surveyed in 10 strata of the 6-cm-thick mat. The diversity of archaea overall was substantial albeit less than the diversity observed previously for bacteria. Archaeal diversity, mainly euryarchaeotes, was highest in the uppermost 2 to 3 mm of the mat and decreased rapidly with depth, where crenarchaeotes dominated. Only 3% of the sequences were specifically related to known organisms including methanogens. While some mat archaeal clades corresponded with known chemical gradients, others did not, which is likely explained by heretofore-unrecognized gradients. Some clades did not segregate by depth in the mat, indicating broad metabolic repertoires, undersampling, or both.
Twelve hour reproducibility of choroidal blood flow parameters in healthy subjects (2004)

These data indicate that in healthy subjects the selected techniques provide adequate reproducibility to be used in clinical studies. Variability may, however, be considerably higher in older subjects or subjects with ocular disease. The higher individual differences in flow parameter readings limit the use of the techniques in clinical practice. To overcome problems with measurement validity, a clinical trial should include as many choroidal blood flow outcome parameters as possible to check for consistency.
Internal shorted patch antenna for a UMTS folder-type mobile phone (2005)

A novel design of feeding and short-circuiting an internal patch antenna for mobile phones is presented. The patch antenna comprises a simple rectangular patch that is fed through and short-circuited to a small ground plane (denoted as antenna ground here) which protrudes from the main or bottom ground of a folder-type mobile phone. With the presence of the small antenna ground, which can function as a shielding wall, the proposed antenna can be placed in close proximity to the RF shielding metal box in the mobile phone, with very small effects on the antenna performances. A design example of the proposed antenna for Universal Mobile Telecommunication System (UMTS) (1920/spl sim/2170MHz) operation is demonstrated. Experimental and simulated results are presented.
Advances in three dimensional printing – state of the art and future perspectives (2006)

Purpose This paper surveys the current state and capabilities of three dimensional printing (3DP). A comprehensive review of 3D Printing applications is presented. The scope of the applications includes design, manufacturing, the medical field and architecture. Design/methodology/approach A large variety of manufacturing applications such as rapid pattern making and rapid tooling using the 3DP process directly or as core technology, as well as further implications in design and engineering analysis, medicine, and architecture are presented and evaluated. Findings Some research issues are also discussed. An attempt, based on the state of the art, to show weaknesses and opportunities, and to draw conclusions about the future of this important process rounds up this paper. Research limitations/implications The scope of this research survey is limited to evaluation and comparison of processes that may be characterised as 3D printing technologies. Practical implications The study is very useful as a basis for matching evaluated 3D printing machine and process capabilities to user requirements, and forms a framework on which future comparative studies can build. Originality/value A comprehensive overview of the capabilities of 3DP processes is presented and evaluated. It shows the application of 3D printing beyond concept modelling. The paper is valuable for researchers as well as individuals, who require adequate and relevant comparative information during decision making.
Selection of Optimal Polypurine Tract Region Sequences during Moloney Murine Leukemia Virus Replication (2000)

Retrovirus plus-strand synthesis is primed by a cleavage remnant of the polypurine tract (PPT) region of viral RNA. In this study, we tested replication properties for Moloney murine leukemia viruses with targeted mutations in the PPT and in conserved sequences upstream, as well as for pools of mutants with randomized sequences in these regions. The importance of maintaining some purine residues within the PPT was indicated both by examining the evolution of random PPT pools and from the replication properties of targeted mutants. Although many different PPT sequences could support efficient replication and one mutant that contained two differences in the core PPT was found to replicate as well as the wild type, some sequences in the core PPT clearly conferred advantages over others. Contributions of sequences upstream of the core PPT were examined with deletion mutants. A conserved T-stretch within the upstream sequence was examined in detail and found to be unimportant to helper functions. Evolution of virus pools containing randomized T-stretch sequences demonstrated marked preference for the wild-type sequence in six of its eight positions. These findings demonstrate that maintenance of the T-rich element is more important to viral replication than is maintenance of the core PPT.
A NEW LIVER FUNCTION TEST (1924)

Various tests, which have been devised to estimate the functional capacity of the liver, have not proved to be of great clinical value. Most of these tests have been used in an attempt to study only one of the several well known functions of the liver. More recently some of the dyes have been employed as permeability tests for liver activity. Among the dyes advocated for this purpose have been methylene blue, 1 congo red, 2 indigo carmine, 3 and phenoltetrachlorphthalein. The last of these dyes has been most extensively studied. Rowntree, Hurwitz and Bloomfield 4 tried to estimate the permeability of the liver by the extraction of the dye from the feces after injection into the blood stream. This method was subject to many sources of error in the collection and extraction of feces and its use has largely been abandoned. The next step in advance was the modification of McNeil, 5 who used
The base-rate fallacy and the difficulty of intrusion detection (2000)

Many different demands can be made of intrusion detection systems. An important requirement is that an intrusion detection system be effective ; that is, it should detect a substantial percentage of intrusions into the supervised system, while still keeping the false alarm rate at an acceptable level. This article demonstrates that, for a reasonable set of assumptions, the false alarm rate is the limiting factor for the performance of an intrusion detection system. This is due to the base-rate fallacy phenomenon, that in order to achieve substantial values of the Bayesian detection rate P(Intrusion***Alarm) , we have to achieve a (perhaps in some cases unattainably) low false alarm rate. A selection of reports of intrusion detection performance are reviewed, and the conclusion is reached that there are indications that at least some types of intrusion detection have far to go before they can attain such low false alarm rates.
Sickle cell membranes and oxidative damage (1986)

Sickle erythrocytes and their membranes are susceptible to endogenous free-radical-mediated oxidative damage which correlates with the proportion of irreversibly sickled cells. The suppression of incubation-induced oxidative stress by antioxidants, free radical scavengers and an iron chelator suggest that oxidation products of membrane-bound haemoglobin contribute towards the pathology of the disease.
Enhanced oral bioavailability of insulin-loaded solid lipid nanoparticles: pharmacokinetic bioavailability of insulin-loaded solid lipid nanoparticles in diabetic rats (2015)

Among the eight different developed formulae (F1-F8), F7 showed an average particle size (99 nm), PDI (0.021), high entrapment of drug (56.5%). The optimized formulation (F7) was further evaluated by FT-IR, DSC, XRD, in vitro release, permeation, stability, bioavailability and pharmacological studies. Insulin-loaded SLNs showed better protection from gastrointestinal environment as evident from the relative bioavailability, which was enhanced five times as compared to the insulin solution. A significant enhancement of relative bioavailability of insulin was observed, i.e. approximately five times of pure insulin solution when loaded in SLN (8.26% versus 1.7% only).
Reference distributions for immunoglobulins A, G, and M: A practical, simple, and clinically relevant approach in a large cohort (1998)

Serum immunoglobulins are measured millions of times each year, yet clinical interpretations remain hampered by inadequate age- and gender-specific reference limits. In order to provide more reliable and comprehensive reference distributions for IgA, IgG, and IgM measurements, we analyzed automated immunoassay values from 115,017 serum samples from northern New England patients (99% Caucasian) who were tested in our laboratory between 1986 and 1995. Measurements were standardized to reference material, CRM 470 (RPPHS). A simple, practical, and clinically relevant approach was used to determine reference distributions for the immunoglobulins over a wide range of ages for males and females. Levels of IgA and IgM varied considerably by age, and by gender for IgM. For each of the analytes, the observed 5th and 95th centiles were symmetric about the median and approximately constant over the entire age range. When immunoglobulin reference values are expressed as multiples of the age- and gender-specific regressed medians, the resulting distributions fit a log-Gaussian distribution well. This finding enables interpretation of serum immunoglobulin measurements using a common unit (multiples of the median) that is independent of age or gender. Insights gained from this study can help improve and simplify the interpretation of immunoglobulin measurements.
Reaction of Zn7Metallothionein with cis- and trans-[Pt(N-donor)2Cl2] Anticancer Complexes:  trans-PtII Complexes Retain Their N-Donor Ligands (2007)

Intrinsic and acquired resistance are major drawbacks of platinum-based cancer therapy. The protein superfamily of cysteine- and ZnII-rich proteins, metallothioneins (MT), efficiently inactivate these antitumor drugs because of the strong reactivity of platinum compounds with S-donor molecules. In this study the reactions of human Zn7MT-2 with twelve cis/trans-[Pt(N-donor)2Cl2] compounds and [Pt(dien)Cl]Cl, including new generation drugs, were investigated and the products characterized. A comparison of reaction kinetics revealed that trans-PtII compounds react faster with Zn7MT-2 than cis-PtII compounds. The characterization of the products showed that while all ligands in cis-PtII compounds were replaced by cysteine thiolates, trans-PtII compounds retained their N-donor ligands, thus remaining in a potentially active form. These results provide an increased understanding of the role of MT in the acquired resistance to platinum-based anticancer drugs.
38.13: a monoclonal antibody directed against a Burkitt's lymphoma-associated antigen and its use as carrier for toxins. (1985)

We have previously described a monoclonal antibody, referred to as 38.13, reacting with most Burkitt's lymphoma (BL) derived lines, both with and without Epstein-Barr virus (EBV), but not reacting with EBV-positive lymphoblastoid cell lines (Wiels et al., 1981, 1982). The antibody reacted with 41 BL lines out of 57 tested. The target antigen, BLA, was shown to be a neutral glycolipid, identified as globotriaosylceramide (Gal alpha 1----4Gal beta 1----4 Glc beta 1----1 ceramide) (Nudelman et al., 1983). This substance is known as the blood group antigen Pk, a normal intermediate in the P-substance synthesis. The 38.13 antibody was covalently linked to either ricin-A chain or gelonin toxin, and its anti-BL specificity remained unaffected. Both immunotoxins were highly cytotoxic for cultured BL cells. The kinetics of the toxic effects of the immunotoxins on these cells appeared to be strikingly fast, since 50% protein synthesis inhibition was achieved after two hours' incubation. These kinetics are similar to those obtained with entire ricin, and clearly different from those observed when using immunotoxins directed against protein antigens (16-30 h). When longer incubation times are used, killing of apparently irrelevant targets was reproducibly observed. These data suggest the presence of a low number of antigenic sites on non-Burkitt cells. The detection of a low number of antigenic sites by immunotoxins directed towards such glycolipid antigens might not be a disadvantage, but might rather permit efficient and rapid killing of a wide variety of tumour cells.