gebhart/patrepeval huggingface dataset:
Transcutaneous Vagus Nerve Stimulation (2011)

Invasive vagus nerve stimulation (VNS) is an approved treatment for drug-resistant epilepsy. Besides its recognised clinical efficacy, there are major drawbacks, such as invasiveness and a great many side effects. Therefore there is a medical demand for transcutaneous VNS (t-VNS®), which combines selective, non-invasive access to vagus nerve afferents with a low risk profile. Both treatments excite thick myelinated fibres of vagus nerve branches that project to the nucleus of the solitary tract in the brainstem. Preclinical data emphasise the equivalent anticonvulsive effects of both methods. Based upon the common mode of action and the first clinical data, the t-VNS device received Conformité Européenne (CE) approval. Besides the approved intended use for drug-resistant epilepsy and depression, a future clinical trial will address the efficacy of t-VNS in chronic pain.
Bovine bone activin enhances bone morphogenetic protein-induced ectopic bone formation. (1992)

A 25-kDa homodimeric protein was purified from demineralized bovine bone extract and identified as activin A. The bovine bone activin enhanced formation of ectopic bone in rat subcutis when implanted in combination with partially purified bovine bone morphogenetic protein (BMP-2, BMP-3) in collagen/ceramic carrier. The implants, removed at 14 days, contained markedly elevated levels of alkaline phosphatase activity. Histological examination revealed an extensive formation of woven bone with very little cartilage. In contrast, a combination of transforming growth factor-beta 2 and BMP promoted formation of bone with an abundance of cartilage. The implants with BMP alone exhibited some osteoinductive activity, while the implants with activin alone showed no activity. These results demonstrate that bone is a rich source of activin and that activin plays an important role in modulating bone formation.
Disruption of Cancer Cell Replication by Alternating Electric Fields (2004)

Abstract Low-intensity, intermediate-frequency (100–300 kHz), alternating electric fields, delivered by means of insulated electrodes, were found to have a profound inhibitory effect on the growth rate of a variety of human and rodent tumor cell lines (Patricia C, U-118, U-87, H-1299, MDA231, PC3, B16F1, F-98, C-6, RG2, and CT-26) and malignant tumors in animals. This effect, shown to be nonthermal, selectively affects dividing cells while quiescent cells are left intact. These fields act in two modes: arrest of cell proliferation and destruction of cells while undergoing division. Both effects are demonstrated when such fields are applied for 24 h to cells undergoing mitosis that is oriented roughly along the field direction. The first mode of action is manifested by interference with the proper formation of the mitotic spindle, whereas the second results in rapid disintegration of the dividing cells. Both effects, which are frequency dependent, are consistent with the computed directional forces exerted by these specific fields on charges and dipoles within the dividing cells. In vivo treatment of tumors in C57BL/6 and BALB/c mice (B16F1 and CT-26 syngeneic tumor models, respectively), resulted in significant slowing of tumor growth and extensive destruction of tumor cells within 3–6 days. These findings demonstrate the potential applicability of the described electric fields as a novel therapeutic modality for malignant tumors.
Rosacea fulminans in a patient with Crohn's disease: a case report and review of the literature (2000)

Rosacea fulminans is a rare disorder of unknown cause that mainly affects postadolescent women, with abrupt onset and disfiguring course if left untreated. The simultaneous occurrence of rosacea fulminans and inflammatory bowel disease is rare and has been reported predominantly in the setting of ulcerative colitis. We describe here a case of rosacea fulminans in a patient with Crohn's disease and discuss a possible association between the two conditions.
Analysis of rice Act1 5' region activity in transgenic rice plants. (1991)

The 5' region of the rice actin 1 gene (Act1) has been developed as an efficient regulator of foreign gene expression in transgenic rice plants. To determine the pattern and level of rice Act1 5' region activity, transgenic rice plants containing the Act1 5' region fused to a bacterial beta-glucuronidase (Gus) coding sequence were generated. Two independent clonal lines of transgenic rice plants were analyzed in detail. Quantitative analysis showed that tissue from these transgenic rice plants have a level of GUS protein that represents as much as 3% of total soluble protein. We were able to demonstrate that Act1-Gus gene expression is constitutive throughout the sporophytic and gametophytic tissues of these transgenic rice plants. Plants from one transgenic line were analyzed for the segregation of GUS activity in pollen by in situ histochemical staining, and the inheritance and stability of Act1-Gus expression were assayed in subsequently derived progeny plants.
Transformed root cultures for biotechnology (1997)

Abstract This review is concerned with the application of hairy roots, i.e. plant roots formed from plant cells after transformation by Agrobacterium rhizogenes for the production of bioactive compounds. Transformed root cultures have been established from numerous species of dicotyledonous plants. The plants, as well as the main products accumulated in hairy root cultures derived from these plants, are listed in this paper. Data are presented on novel compounds, hitherto detected only in transformed roots but not occurring in the corresponding intact plants. The possible use of hairy root cultures for the over‐production of secondary metabolites and biotransformation of chemicals is discussed. In order to enhance the productivity of hairy root cultures, various methods have been derived, and optimized procedures are proposed. They include selection of high‐producing clones, elicitation, composition of growth media, culture conditions and genetic approach. Hairy roots usually store secondary metabolites in vacuoles inside the cells. Therefore, several methods have been used to increase the amount of products released into the medium. Unfortunately, no general procedure is known that works in all cases, and the excretion behaviour of hairy root cultures varies from one species to another and even within one species from one clone to another. Special attention is given to the cultivation methods and bioreactor systems for hairy root cultures. Hairy roots are cultivated usually in shake flasks; however, shake flask culture is not suitable for the complex optimization and continuous control of the culture conditions. In this paper, we are going to present bioreactors proposed for the cultivation of hairy roots under more or less controlled conditions. Modifications of typical bacterial bioreactors, i.e. stirred tanks, airlift loop reactors and other constructions, are presented. A very special type of bioreactor providing good conditions for loose root mass multiplication without oxygen or substrate limitations, is the mist bioreactor. Nowadays, it is practically impossible to select the one best bioreactor type for hairy root culture.
Multivesicular Liposome (DepoFoam) Technology for the Sustained Delivery of Insulin-Like Growth Factor-I (IGF-I) (1998)

Insulin-like Growth Factor I (IGF-I), a 7.65 kD protein which has a variety of metabolic functions, is being evaluated for its therapeutic benefit in several disease states. To sustain therapeutic blood levels in a number of these instances, IGF-I needs to be administered repeatedly. The objective of these studies was the development of a sustained-release depot delivery system for this protein which would replace repeated administration. Using a multivesicular liposome drug delivery system (DepoFoam), sustained delivery kinetics have been observed for IGF-I. IGF-I was successfully encapsulated in this system with good efficiency. The integrity of the encapsulated protein was maintained, as characterized by physiochemical (HPLC, SDS-PAGE), and by biological methods (mitogenic activity). The DepoIGF-I particles were also characterized by their morphology (particles were smooth, multivesicular, and there was no debris), particle size (ranged from 18 to 20 microm), and in vitro and in vivo release kinetics of IGF-I. The DepoIGF-I particles released the protein drug in a sustained manner both in vitro and in vivo without a rapid initial release, and the released protein maintained its structural integrity and biological activity. The in vitro studies in human plasma at 37 degreesC showed that the DepoIGF-I particles released IGF-I slowly over several days; 70-80% of the protein was released in 6-7 days. In a pharmacokinetic in vivo study, after subcutaneous injections in rats, IGF-I levels were sustained for 5-7 days with DepoIGF-I formulation, whereas IGF-I in the free form was cleared in 1 day. DepoFoam technology provides a pharmaceutically useful system of sustained delivery for proteins, which can be extended to other therapeutic macromolecules.
Mutational analysis and properties of the msbA gene of Escherichia coli, coding for an essential ABC family transporter (1996)

The htrB gene was discovered because its insertional inactivation interfered with Escherichia coli growth and viability at temperatures above 32.5 degrees C, as a result of accumulation of phospholipids. The msbA gene was originally discovered because when cloned on a low-copy-number plasmid vector it was able to suppress the temperature-sensitive growth phenotype of an htrB null mutant as well as the accumulation of phospholipids. The msbA gene product belongs to the superfamily of ABC transporters, a universally conserved family of proteins characterized by a highly conserved ATP-binding domain. The msbA gene is essential for bacterial viability at all temperatures. In order to understand the physiological role of the MsbA protein, we mutated the ATP-binding domain using random PCR mutagenesis. Six independent mutants were isolated and characterized. Four of these mutations resulted in single-amino-acid substitutions in non-conserved residues and were able to support cell growth at 30 degrees C but not at 43 degrees C. The remaining two mutations behaved as recessive lethals, and resulted in single-amino-acid substitutions in Walker motif B, one of the two highly conserved regions of the ATP-binding domain. Despite the fact that neither of these two mutant proteins can support E. coli growth, they both retained the ability to bind ATP in vitro. In addition, we present evidence to show that N-acetyl [3H]-glucosamine, a precursor of lipopolysaccharides, accumulates at the non-permissive temperature in the inner membrane of either htrB null or msbA conditional lethal strains. Translocation of the precursor to the outer membrane is restored by transformation with a plasmid containing the wild-type msbA gene. A possible role for MsbA as a translocator of lipopolysaccharides or its precursors is discussed.
A Promoter Relay Mechanism for Sequential Gene Activation (1998)

The effect of DNA supercoiling on gene expression is dependent not only on specific genes but also on the sequence context of the genes. This position-dependent supercoiling effect on gene activation is best illustrated in the study of the suppression of the leu-500 mutation of the leuABCD operon in a Salmonella typhimurium topA mutant. In this communication, we report a novel promoter relay mechanism whereby several genes are sequentially expressed in a position-dependent manner: the ilvIH promoter (pilvIH) activates a cryptic leuO promoter (pleuO) located between the two divergently arrayed ilvIH and leu-500 promoters. Both the cis-acting pleuO activity and the trans-acting LeuO protein are necessary for subsequent activation of the leu-500 promoter (pleu-500). Furthermore, pleuO can be functionally replaced with the inducible tac promoter (ptac) for leu-500 activation, suggesting that transcription-driven DNA supercoiling underlies the relay mechanism. This is the first example of several related genes communicating via a promoter relay mechanism for their coordinated expression.
Combination of epidermal growth factor receptor targeted therapy with radiation therapy for malignant gliomas (2003)

Glioblastoma multiforme (GBM) are extremely aggressive brain tumors characterized by resistance to standard treatment modalities including surgery, radiation therapy and chemotherapy. While radiation therapy is the standard treatment after surgical resection, these tumors invariably recur and are associated with a uniformly dismal prognosis. Cytotoxic chemotherapy has failed to improve on the modest gains conferred by radiation therapy. Our understanding of the molecular events driving gliomagenesis has led to the recognition of frequent alterations in the epidermal growth factor receptor (EGFR) pathway, leading to increased aggressiveness and a poorer prognosis. Based on the importance of EGFR in the development of malignancy in multiple tumor types, several classes of novel therapeutic agents have been developed that specifically target EGFR. This review outlines the relevance of normal and aberrant EGFR signaling in the biology of gliomas, the strategies for inhibiting EGFR activity and the rationale for combining EGFR inhibitors with radiation therapy in the treatment of GBM.
Epitope mapping of a protein using the Geysen (PEPSCAN) Procedure (1994)

Immunity to many diseases is dependent on the ability of the host™s antibodies to recognize foreign antigens, such as surface proteins or toxins, and bind them tightly and specifically. This binding is an important aspect of the immune response, and it is often required for subsequent immune processes that ultimately result in re-establishment of a diseasefree state.
Detection of numerical chromosome anomalies in interphase cells of ovarian carcinomas using fluorescence in situ hybridization (1996)

Fluorescence in situ hybridization was used in interphase cells of 30 ovarian carcinomas to detect numerical changes in copy number of 13 different centromeres (1, 2, 3, 4, 6, 7, 8, 10, 11, 12, 17, 18, and X). Thirty-seven percent of samples (11/30) were near diploid and demonstrated only minor changes in centromere copy number, involving gain and/or loss of one or a few centromeres. The most common changes included loss of centromeres 4,6, 17, and 18 and gain of centromere 1. The remaining 63% of samples were hyperdiploid and demonstrated a general increase in copy number of most or all centromeres examined. Among these samples, the centromere of chromosome I was most often found to be at higher copy number. Centromeres that were less often at increased copy or deleted within the hyperdiploid samples include centromeres 4, 17, 18, and X. These results suggest that tumor-suppressor genes that are located on chromosomes 4, 6, 17, and 18 may be involved in the development and progression of ovarian cancer.
Sequence-specific error profile of Illumina sequencers (2011)

We identified the sequence-specific starting positions of consecutive miscalls in the mapping of reads obtained from the Illumina Genome Analyser (GA). Detailed analysis of the miscall pattern indicated that the underlying mechanism involves sequence-specific interference of the base elongation process during sequencing. The two major sequence patterns that trigger this sequence-specific error (SSE) are: (i) inverted repeats and (ii) GGC sequences. We speculate that these sequences favor dephasing by inhibiting single-base elongation, by: (i) folding single-stranded DNA and (ii) altering enzyme preference. This phenomenon is a major cause of sequence coverage variability and of the unfavorable bias observed for population-targeted methods such as RNA-seq and ChIP-seq. Moreover, SSE is a potential cause of false single-nucleotide polymorphism (SNP) calls and also significantly hinders de novo assembly. This article highlights the importance of recognizing SSE and its underlying mechanisms in the hope of enhancing the potential usefulness of the Illumina sequencers.
Covalent Attachment of a Nickel Nitrilotriacetic Acid Group to a Germanium Attenuated Total Reflectance Element (2004)

The surface of a germanium internal reflectance element (IRE) was modified to bind 6X-histidine (his)-tagged biomolecules. The step-by-step surface modification was monitored via single-pass attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FT-IR). Initially an adlayer of 7-octenyltrimethoxysilane (7-OTMS) was formed on the Ge crystal through the surface hydroxyl groups, which were produced via ozonolysis of the Ge surface. The vinyl moiety of 7-OTMS was oxidized to a carboxylic acid, which was activated by 1,1'-carbonydiimidazole (CDI) to produce a labile imidazole. The labile imidazole that resulted from the CDI coupling was then displaced by the primary amine of nitrilotriacetic acid (NTA). Nickel sulfate was added to the system, and it coordinated with the three carbonyl groups and the nitrogen on NTA, thus leaving the ability of Ni to coordinate with two adjacent histidine residues. Binding of his-tagged biotin to nickel nitrilotriacetic acid (Ni-NTA) was observed by ATR-FT-IR spectroscopy. The surface modification method presented in this paper had minimal nonspecific binding, the Ni-NTA surface was reusable if stored properly, and complete removal of the organic surface was achievable.
Personal multi-media multi-point communication services for broadband networks (2003)

Discuss attributes for multimedia multipoint communications services and describe a prototype system which is targeted at testing service concepts and evolving technologies that will stimulate the widespread deployment of multimedia group communications in future broadband networks. Personal teleconferencing in various forms is included in this service environment. A framework is proposed for categorizing various forms of communications media interrelationships. Users are provided with the flexibility to invoke each medium at any time and control various modes of media integration dynamically. An experimental graphical user interface has been proposed and implemented in the X Window System. The attributes of a high-end workstation matched to the proposed service are discussed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The alpha and beta chains of avian retrovirus reverse transcriptase independently expressed in Escherichia coli: characterization of enzymatic activities. (1988)

Reverse transcriptase of the avian sarcoma and leukosis retroviruses is a heterodimer composed of a 63-kDa alpha and a 95-kDa beta polypeptide chain, both of which are encoded in the pol gene and are produced by proteolytic processing of a larger precursor. We previously constructed a bacterial expression clone of the entire pol coding region that produces a protein 4 kDa larger than the mature viral beta subunit. By use of this clone and synthetic oligonucleotides to introduce stop codons, two derivatives have been constructed: one that directs synthesis of a protein equivalent to the mature beta subunit and the other that directs synthesis of a protein equivalent to alpha subunit. Predicted amino acid sequences of these proteins differ from their viral counterparts only by an initiator methionine that was added to the N termini for expression in Escherichia coli. Both bacterially expressed proteins exhibit reverse transcriptase activity and appear to function as homodimers. The properties of these proteins resemble those of the viral reverse transcriptase heterodimer; however, the bacterially produced alpha dimer protein could be distinguished from the other proteins by its increased sensitivity to heat inactivation, which also has been reported for the corresponding viral product. These results show that correct folding and expression of enzymatic function does not require formation of a precursor. The alpha and beta clones provide a convenient source of individual pol gene products for further evaluation of their roles in the synthesis and integration of retroviral DNA.
Molecular and Immunological Characterization of Profilin from Mugwort Pollen (2002)

In late summer in Europe, pollen of mugwort is one of the major sources of atopic allergens. No information about the complete molecular structure of any mugwort allergen has been published so far. Here we report the isolation and characterization of mugwort pollen cDNA clones coding for two isoforms of the panallergen profilin. Thirty-six percent of the mugwort-allergic patients tested displayed IgE antibodies against natural and recombinant profilin, and no significant differences were observed in the IgE-binding properties of the isoforms. One profilin isoform was purified to homogeneity and detailed structural analysis indicated that the protein exists in solution as dimers and tetramers stabilized by sulfydryl and/or ionic interactions. Profilin monomers were detectable only after exposure of multimers to harsh denaturing conditions. Dimers and tetramers did not significantly differ in their ability to bind serum IgE from mugwort pollen-allergic patients. However, oligomeric forms might have a higher allergenic potential than monomers because larger molecules would have additional epitopes for IgE-mediated histamine release. Profilin isolated from mugwort pollen also formed multimers. Thus, oligomerization is not an artifact resulting from the recombinant production of the allergen. Inhibition experiments showed extensive IgE cross-reactivity of recombinant mugwort profilin and profilin from various pollen and food extracts.
Enhanced oxygen diffusivity in interfaces of nanocrystalline ZrO 2 ⋅Y 2 O 3 (2003)

First measurements of oxygen grain boundary diffusion coefficients in nanocrystalline yttria-doped ZrO(2) (n-ZrO(2).6.9 mol % Y(2)O(3)) are presented. The (18)O diffusion profiles measured by secondary ion mass spectroscopy are much deeper in the nanocrystalline specimens than in single crystals. An oxygen diffusivity, D(B), in the grain boundaries can be deduced, which is approximately 3 orders of magnitude higher than in single crystals. From the present data the temperature variation of the oxygen grain boundary diffusivity, D(B) = 2.0 x 10(-5) exp (-0.91 eVk(B)T) m(2)s, and the oxygen surface exchange coefficient, k = 1.4 x 10(-2) exp (-1.13 eVk(B)T) ms, are derived.
Structural Guidance of the Photocycle of Channelrhodopsin-2 by an Interhelical Hydrogen Bond (2009)

Channelrhodopsin-2 (ChR2) is a light-gated cation channel and a member of the family of retinylidene photoreceptors. Since the demonstration of light-induced depolarization of ChR2-expressing animal cell membranes, it was increasingly exploited for light triggering of action potentials. ChR2 conducts cations upon light absorption that embodies retinal isomerization as the primary reaction and a structurally unknown opening mechanism. It is evident from spectroscopic data that protonation reactions at the Schiff base are part of the photocycle, comparable to other microbial-type rhodopsins. However, the connection between the processes at the chromophore site and the channel's pore remained enigmatic. Here, we use slow mutants of ChR2 that we generated by disturbing a postulated hydrogen bond when mutating C128 in the transmembrane (TM) helix 3 and D156 in TM helix 4. The lifetime of the mutants' open state is increased more than 100 times. We investigated the spectral properties of the slow mutants. Whereas the deprotonation of the Schiff base (yielding P390) occurs on the same time scale as that of the wild type, reprotonation to P520 is retarded in the slow mutants and their photocycle is split, leading to the presence of two photointermediates, P390 and P520, in the open state. The photoreactions of P390 and P520 lead to a quenching of the current in electrophysiological measurements. We conclude that the putative hydrogen bond between C128 and D156 is an important structural determinant of the channel's closing reaction. Furthermore, we show that the D156A mutant is even more suitable for light control of excitable cells than C128A.