gebhart/patrepeval huggingface dataset:
Activatable quantum dots for mouse non-invasive fluorescence imaging (2007)

Non-invasive near infrared fluorescence imaging of mice models is a very attractive tool for fastening the development of new therapeutics. Two classes of labels exist for the near infrared domain: organic dyes and quantum dots (QDs). QDs are inorganic luminescent semi-conductor nano-crystals which display very attractive optical features. They are now commercially available for in vivo mouse tests, and new compositions with less toxic elements are currently being developed. The concept of activatable probes, which fluorescence is activated specifically upon the biological process to be visualized, has also been demonstrated to improve the fluorescence image contrast. The construction of activatable probes based on quantum dot labels has therefore been undertaken. Commercial PEGylated quantum dots bearing around 80-100 amino pending groups are used. Long PEG chains are demonstrated to be essential in order to increase the blood circulation time of the particles and avoid their massive storage into the liver. The amino groups coating the QD surface can be used for their further functionalization by either a tumor-targeting ligand, a cleavable spacer bearing a fluorescence inhibitor I, or both. Functionalization of 80% of the amino groups by the inhibitors I leads to more than 99% fluorescence quenching. Cleavable spacers X-L-S-S-L'-I in which S-S is a disulfide bond cleavable by cell internalization, and X a chemical group for QD grafting have been synthesized. The functionalization of the QD by 12 cleavable spacers leads to more than 85% fluorescence inhibition, which can be recovered upon cleavage of the disulfide bonds.
Redox Imbalance and Its Control in HIV Infection (2002)

Human immunodeficiency virus (HIV)-infected individuals are suffering from systemic oxidative stress. Reactive oxygen species act as second messengers for the activation of nuclear factor-kappaB (NF-kappaB), which augments the replication of HIV. Intracellular levels of glutathione (GSH), a major cytosolic antioxidant, in T cells decrease during the disease progression. Another redox-regulating molecule, thioredoxin (TRX), is also transiently down-regulated in the cells by acute HIV infection. In contrast, plasma levels of TRX are elevated in the late stage of HIV infection. Intracellular GSH and plasma TRX can be biomarkers to predict the prognosis of the disease. N-Acetylcysteine (NAC), a prodrug of cysteine that is necessary for GSH synthesis, has been used for HIV infection to prevent the activation of NF-kappaB and the replication of HIV. NAC shows some beneficial effects for HIV-infected individuals, although the intracellular GSH levels in lymphocytes are not significantly restored. The control of imbalanced redox status by antioxidants may be beneficial for the quality of life in HIV infection even in the era after the effective therapy with protease inhibitors has been applied. Redox control will be an important therapeutic strategy for oxidative stress-associated disorders including HIV infection.
Genetics of autosomal recessive non‐syndromic mental retardation: recent advances (2007)

The identification of the genes mutated in autosomal recessive non-syndromic mental retardation (ARNSMR) has been very active recently. This report presents an overview of the current knowledge on clinical data in ARNSMR and progress in research. To date, 12 ARNSMR loci have been mapped, and three genes identified. Mutations in known ARNSMR genes have been detected so far in only a small number of families; their contribution to mental retardation in the general population might be limited. The ARNSMR-causing genes belong to different protein families, including serine proteases, Adenosine 5'-triphosphate-dependent Lon proteases and calcium-regulated transcriptional repressors. All of the mutations in the ARNSMR-causing genes are protein truncating, indicating a putative severe loss-of-function effect. The future objective will be the development of diagnostic kits for molecular diagnosis in mentally retarded individuals in order to offer at-risk families pre-natal diagnosis to detect affected offspring.
Radioimmunoscintigraphy and radioimmunotherapy in cancer: principles and application. (2000)

Radioimmunoscintigraphy (RIS) and radioimmunotherapy (RIT) are recent approaches in the diagnosis and treatment of cancer. They take advantage of the antibody specificity of tumor surface antigens and of the emitted radiation from suitable radioisotopes, as a means of imaging (RIS) or therapy (RIT). Research into RIS and RIT radiolabelled agents remains an ongoing process. Principles governing the choice of radionuclides, labelling protocols, antibody suitability, and optimization of "tumor to normal tissue ratios" are the same for both RIS and RIT. The investigational stages of the labelled product, prior to clinical application, are also the same. These stages include radiochemical and radiobiological evaluation as well as determination of immunoreactivity. Furthermore, RIS may be considered as the first stage in development, before progressing on to RIT. Differences between RIS and RIT are associated with the application of each technique, that is, the type of radiation emitted by the isotope, dosage regimens, haematopoetic toxicity and the appearance of human antimurine antibody response (HAMA). RIS has found widespread clinical application, detecting a variety of tumors. However, its potential lies in patient management and in detecting metastases. On the other hand RIT is still in its infancy. It appears promising, and for the moment is used as a complementary technique to surgery and/or chemotherapy in clinical trials on cancer treatment. Finally, incorporation of these basic principles arising from past experiences, into the design of RIT trials improve responses.
The mammalian secreted RNases: Mechanisms of action in host defence (2012)

The mammalian ribonucleaseA family comprises a large group of structurally similar proteins which are secreted by a range of tissues and immune cells. Their physiological role is unclear. It has been suggested that some of these RNases contribute to host defence, notably eosinophil-derived neurotoxin, eosinophil cationic protein, eosinophil-associated RNases, RNase4, angiogenin (RNase5), RNase7, RNase8 and bovine seminal RNase. This review summarises data supporting the involvement of these proteins in host defence, focusing on their antimicrobial, cytotoxic and immunomodulatory activities. The extent to which the data support possible mechanisms of action for these proteins is discussed. This compilation of findings and current hypotheses on the physiological role of these RNases will provide a stimulus for further research and development of ideas on the contribution of the RNases to host defence.
Inhibition of binding ofHelicobacter pylorito the glycolipid receptors by probioticLactobacillus reuteri (2002)

We examined the competition of binding of Lactobacillus reuteri and Helicobacter pylori to gangliotetraosylceramide (asialo-GM1) and sulfatide which are putative glycolipid receptor molecules of H. pylori, and identified a possible sulfatide-binding protein of the L. reuteri strain. Among nine L. reuteri strains, two (JCM1081 and TM105) were shown to bind to asialo-GM1 and sulfatide, and to inhibit binding of H. pylori to both glycolipids by a thin layer chromatogram-overlay assay using biotin-labeled bacterial cells. The extract from the bacterial cells of strain TM105 with several detergents, including octyl beta-D-glucopyranoside, retained binding to both glycolipids and also inhibited H. pylori binding, suggesting that a binding inhibitor(s) is associated with the bacterial cell surface. When the cell extract was applied to the agarose gel immobilized galactose 3-sulfate corresponding to the structure of sugar moieties of sulfatide, an approximately 47-kDa protein was found to bind to the gel. This observation strongly suggested that inhibition by selected L. reuteri strains help to prevent infection in an early stage of colonization in H. pylori and proposed that L. reuteri strains sharing glycolipid specificity with H. pylori have a potential as probiotics.
Use of anti-idiotypic antibodies to establish that monoclonal antibody 7H11D6 binds to the alpha 2-macroglobulin receptor recognition site. (1988)

Studies were performed to determine if monoclonal antibody 7H11D6 binds to the region of alpha 2-macroglobulin (alpha 2M) that interacts with cell-surface receptors. F(ab')2 fragments prepared from this antibody delayed the in vivo clearance of alpha 2M-trypsin complexes from the murine circulation and blocked the in vitro binding of 125I-labeled alpha 2M-trypsin to rat kidney fibroblasts. Chemical modification studies revealed that the epitope region for 7H11D6 is sensitive to modification of the inhibitor with cis-dichlorodiammineplatinum (II). To determine if the epitope for 7H11D6 is comprised of residues involved in the alpha 2M receptor determinant, anti-idiotypic antibodies against 7H11D6 were prepared. A competitive enzyme-linked immunosorbent assay demonstrated that the anti-idiotypic IgG competed with alpha 2M-trypsin complexes for binding to 7H11D6. The anti-idiotypic IgG inhibited the binding of 125I-labeled alpha 2M-trypsin complexes to normal rat kidney fibroblasts, and a Kd of 194 pM for the binding of the anti-idiotype to these cells was derived from a fit of the data to a model involving a single class of sites. Binding of the anti-idiotypic IgG to the alpha 2M receptor provides unequivocal evidence that 7H11D6 is binding to residues within the receptor recognition site on alpha 2M and not merely to residues sufficiently close to that region to cause steric hindrance.
The critical region of overlap defining the AZFa male infertility interval of proximal Yq contains three transcribed sequences. (1999)

The position of deletion breakpoints in a series of four AZFa male infertility patients has been refined using new markers derived from BAC clone DNA sequence covering the AZFa male infertility interval. The proximal half of the AZFa interval is occupied by pseudogene sequences with homology to Xp22. The distal half contains an anonymous expressed sequence tag (named AZFaT1) found transcribed in brain, testis, and skeletal muscle and the DFFRY and DBY genes. All the patients have AZFaT1 and DFFRY deleted in their entirety and three patients additionally have DBY deleted. The three patients with AZFaT1, DFFRY, and DBY deleted show a severe Sertoli cell only syndrome type I phenotype, whereas the patient that has retained DBY shows a milder oligozoospermic phenotype. The expression of DBY in a cell line from this latter patient is unaltered; this shows that it is the loss of genes lying within the deletion that is responsible for the observed oligozoospermia. RT-PCR analysis of mouse testis RNA from normal and XXSxr(a) mice (devoid of germ cells) has shown that Dby is expressed primarily in somatic cells and that the level of expression is unaltered during germ cell differentiation. This contrasts with Dffry where no transcripts are detectable in XXSxr(a) mouse testis and expression occurs specifically in testis mRNA in a germ cell dependent fashion.
Why are Most Funds Open-End? Competition and the Limits of Arbitrage (2005)

The majority of asset-management intermediaries (e.g., mutual funds, hedge funds) are structured on an open-end basis, even though it appears that the open-end form can be a serious impediment to arbitrage. I argue that when funds compete to attract investors' dollars, the equilibrium degree of open-ending in an economy can be excessive from the point of view of these investors. One implication of the analysis is that, even absent short-sales constraints or other frictions, economically large mispricings can coexist with rational, competitive arbitrageurs who earn small excess returns.
Tandem Optimization of Target Activity and Elimination of Mutagenic Potential in a Potent Series of N‐Aryl Bicyclic Hydantoin‐Based Selective Androgen Receptor Modulators. (2007)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Expression of the human interferon–γ cDNA in yeast (1983)

Several plasmids which direct the expression of human interferon-gamma (IFN-gamma) cDNA in the yeast Saccharomyces cerevisiae under the transcriptional control of the 3-phosphoglycerate kinase (PGK) promoter have been constructed. Up to 25 x 10(6) units per liter culture of biologically active IFN-gamma are synthesized in yeast transformed with these expression plasmids. The amount of IFN-gamma mRNA in yeast transformed with the IFN-gamma expression plasmids is much lower than the amount of PGK mRNA present when the PGK gene and promoter are inserted on a similar plasmid. The major and three minor sites of transcription initiation have been localized. The major starting point of the IFN-gamma mRNA is at 4 basepairs upstream of the PGK mRNA start. All transcription starts map at an ApG as does PGK mRNA. The yeast IFN-gamma mRNA terminates in a specific segment of the 3' untranslated region of the IFN-gamma cDNA. The polyadenylation site at about 182-184 nucleotides 3' of the IFN-gamma stop codon is preceded by a sequence which is very similar to a sequence proposed to be involved in transcription termination and polyadenylation (49).
Dispersion compensation in whispering-gallery modes (2003)

We show that manipulation by a spatial profile of the refractive index of a circularly symmetric dielectric cavity results in a novel way of fine tuning frequency separations as well as spatial localizations of high-Q whispering-gallery modes excited in the cavity. The method permits dispersion compensation in the modes (spectrum equalization), diminishes the quality-factor limitation by surface roughness and contamination, and allows critical coupling to ultra-high-Q modes without maintaining an air gap with evanescent couplers.
Role of positive charge on the amino-terminal region of the signal peptide in protein secretion across the membrane. (1982)

The positively charged amino-terminal region of the signal peptide has been proposed to have an important role at an initial step of protein secretion across the membrane (loop model). To test this hypothesis, the charge on the amino-terminal region of the signal peptide of the prolipoprotein of the Escherichia coli outer membrane was altered by using synthetic oligonucleotides from +2 to +1, 0, and -1 by guided site specific mutagenesis of a plasmid DNA carrying an inducible lipoprotein gene. The wild-type sequence of this sectio, Met-Lys-Ala-Thr-Lys (+2), was thus changed to Met-Lys-Asp-Thr-Lys (I-1; +1), Met-Ala-Thr-Lys (I-2; +1), Met-Asp-Thr-Lys (I-3; 0), and Met-Glu-Asp-Thr-Lys (I-4; -1). After induction of lipoprotein production, cells were pulse labeled with [35S]methionine for 10 sec. The lipoprotein of I-1, I-2, and I-3 was assembled in the membrane, although the rates of lipoprotein production progressively decreased as the charge on the signal peptide became more negative. Conversely, in the case of I-4, only a small amount of lipoprotein assembled in the membrane while a large amount of glycerol-unmodified prolipoprotein accumulated in the cytoplasm. This soluble prolipoprotein was gradually and posttranslationally secreted across the membrane to be modified and assembled in the membrane. These results indicate that the positively charged amino-terminal region of the signal peptide plays an important role in efficient protein secretion across the membrane.
Uncoupling of the order of the S and M phases: effects of staurosporine on human cell cycle kinases (1997)

The protein kinase inhibitor staurosporine (SSP) was employed to study the involvement of kinases in human cell cycle progression.Thirty to 100 ng/ml SSP blocks entry into S phase and M phase.Lack of entry into S phase is due to impaired activity of the retinoblastoma protein kinase.The requirement for any of the SSP-sensitive kinases for cell cycle progression can be abrogated in tumour cells.Therefore, these kinases act in a checkpoint network negatively controlling the initiation of S phase, M phase and cytokinesis, rather than being inherent parts of a substrate-product chain required for the initiation of the cell cycle phases.As a consequence of the lack of certain checkpoint effectors, tumour cells may endoreduplicate or binucleate in the presence of SSP.The latter processes, as well as meiosis, are naturally occurring in specialized cell types, leading to the idea that this checkpoint network controls the order of the cell cycle phases in normal cells.A model is presented where the cell cycle is envisioned as two independently running cycles, the S and the M cycle, which are controlled by intra and intercycledependent checkpoints in human somatic cells.The model accounts for the dependency of S and M phase initiation on the successful completion of the previous M and S phase, respectively, as well as entry into a resting state.The cell cycle of somatic cells is characterized by the presence of checkpoints ensuring that an earlier event is successfully finished before a later event is initiated (Hartwell & Weinert 1989).Checkpoints may employ positively or negatively acting effectors.In the latter case, they are not part of the substrate-product chains required for the initiation of the cell cycle phases.Some of the checkpoints are silent in embryonic cells, which could in principle lead to, e.g.initiation of M phase before S phase was completed.This situation, referred to as the 'completion problem' (Murray 1992), may be avoided because initiation of, e.g.M phase may require time-dependent processes to occur, such that S phase is traversed before M phase is initiated.Candidates for gene products performing negative checkpoint-functions in mammals, i.e. gene products which are not strictly required for progression through the early embryonic cell cycles, have been suggested from experiments with transgenic mice.These candidates include the retinoblastoma gene product (pRB, Lee et al.
Ethnomedicinal Uses of Achyranthes Aspera L. (Amarantaceae) in Management of Gynaecological Disorders in Western Uttar Pradesh (India) (2005)

This communication records the ethno-medicinal uses of Achyranthes aspera in management of gynecological disorders in rural areas of Aligarh, Badaun, Bulandshahar, Farrukhabad and Hatharas districts of Western Uttar Pradesh, India. The claims were gathered by interviewing traditional healers, especially women, of the study area. Attempt was made to verify the efficacy of claims with actual beneficiaries, though it was not possible in all cases due to social customs. A total of twenty-three claims are recorded and twelve of them appear to be hitherto unknown.
Human C-type natriuretic peptide. Characterization of the gene and peptide. (1992)

We isolated the human C-type natriuretic peptide gene and identified the peptide in the brain. The human C-type natriuretic peptide gene appeared to be composed of at least two exons and one intron. In the 5'-flanking region, there is an array of cis elements (an inverted CCAAT box, two GC boxes, and a cyclic AMP response element-like sequence) that is not present in upstream sequences of the atrial and brain natriuretic peptide genes. Analysis of the deduced amino acid sequence revealed that human prepro C-type natriuretic peptide comprises 126 amino acids and that the C-terminal 22-residue peptide (G-L-S-K-G-C-F-G-L-K-L-D-R-I-G-S-M-S-G-L-G-C) preceded by Lys-Lys is identical to the porcine counterpart. However, replacement of two amino acids took place in the C-terminal 53-residue sequence, corresponding to another endogenous form of the peptide. Reverse-phase high-performance liquid chromatography coupled with a radioimmunoassay for C-type natriuretic peptide demonstrated that it occurs in the human brain. C-type natriuretic peptide-like immunoreactivity was detected in discrete regions of the human brain, and its level was 10-fold higher than the atrial and brain natriuretic peptide levels, raising the possibility that C-type natriuretic peptide is the major natriuretic peptide in the human brain.
Beyond the Superhighway: Exploiting the Internet with Medical Informatics (1997)

As in other areas of society, the Internet and the World Wide Web are becoming important topics in medical informatics. This is evident from the recent American Medical Informatics Association's 1996 Annual Fall Symposium, where the theme was "Beyond the Superhighway: Exploiting the Internet with Medical Informatics." Of the over 330 papers and abstracts published in the Proceedings, one third dealt with the Internet and/or the Web. In some cases, system developers demonstrated how this technology can do old tasks in new ways. In other cases, researchers described new tasks that are now possible with this technology. Still others examined this technology to show how it can be evaluated and improved. This paper summarizes their accomplishments.
The Function of Leptin in Nutrition, Weight, and Physiology (2002)

Recent advances indicate that a robust physiologic system acts to maintain relative constancy of weight in mammals. A key component of this system is leptin. Leptin is an adipocyte hormone that functions as the afferent signal in a negative feedback loop regulating body weight. In addition, leptin functions as a key link between nutrition and the function of most, if not all other physiologic systems. When at their set point, individuals produce a given amount of leptin and in turn maintain a state of energy balance. Weight gain results in an increased plasma leptin level, which elicits a biologic response characterized in part by a state of negative energy balance. Weight loss among both lean and obese subjects results in decreased plasma levels of leptin, which lead to a state of positive energy balance and a number of other physiologic responses. In humans, both the intrinsic sensitivity to leptin and its rate of production vary and both appear to contribute to differences in weight. Further studies of leptin, its receptor, and the molecular components of this system are likely to have a major impact on our understanding of obesity and the interplay between nutrition and physiology.
Electroporation Therapy of Head and Neck Cancer (1998)

The purpose of this paper is to introduce the concept of electroporation therapy and present our results from using this new technique combined with intralesional bleomycin in head and neck cancer patients. Electroporation therapy is a technique wherein high-voltage electric impulses delivered into a neoplasm transiently increase cell membrane permeability to large molecules, including cytotoxic agents. In this phase I/II study, extremely low-dose bleomycin sulfate was electroporated into head and neck malignant neoplasms in 10 patients. Tumor responses included 2 nonresponders, 3 partial responders, and 5 complete responders, with a mean follow-up of 40 weeks. We conclude that this technique offers promising possibilities in the local treatment of head and neck cancer.