gebhart/patrepeval huggingface dataset:
Comparison of the efficacy and tolerability of 3% diclofenac sodium gel and 5% imiquimod cream in the treatment of actinic keratosis (2008)

The two drugs were found to be equally effective and safe in the treatment of actinic keratosis but complete remission was very low. Therefore, topical treatments with these two drugs were not seen to be completely effective, and combined therapies and further studies are needed.
Retroviral Transduction of T-cell Receptors in Mouse T-cells (2010)

T-cell receptors (TCRs) play a central role in the immune system. TCRs on T-cell surfaces can specifically recognize peptide antigens presented by antigen presenting cells (APCs). This recognition leads to the activation of T-cells and a series of functional outcomes (e.g. cytokine production, killing of the target cells). Understanding the functional role of TCRs is critical to harness the power of the immune system to treat a variety of immunology related diseases (e.g. cancer or autoimmunity). It is convenient to study TCRs in mouse models, which can be accomplished in several ways. Making TCR transgenic mouse models is costly and time-consuming and currently there are only a limited number of them available. Alternatively, mice with antigen-specific T-cells can be generated by bone marrow chimera. This method also takes several weeks and requires expertise. Retroviral transduction of TCRs into in vitro activated mouse T-cells is a quick and relatively easy method to obtain T-cells of desired peptide-MHC specificity. Antigen-specific T-cells can be generated in one week and used in any downstream applications. Studying transduced T-cells also has direct application to human immunotherapy, as adoptive transfer of human T-cells transduced with antigen-specific TCRs is an emerging strategy for cancer treatment. Here we present a protocol to retrovirally transduce TCRs into in vitro activated mouse T-cells. Both human and mouse TCR genes can be used. Retroviruses carrying specific TCR genes are generated and used to infect mouse T-cells activated with anti-CD3 and anti-CD28 antibodies. After in vitro expansion, transduced T-cells are analyzed by flow cytometry.
Optimization of Peptide Hydroxamate Inhibitors of Insulin-Degrading Enzyme Reveals Marked Substrate-Selectivity (2013)

Insulin-degrading enzyme (IDE) is an atypical zinc-metallopeptidase that degrades insulin and the amyloid ß-protein and is strongly implicated in the pathogenesis of diabetes and Alzheimer's disease. We recently developed the first effective inhibitors of IDE, peptide hydroxamates that, while highly potent and selective, are relatively large (MW > 740) and difficult to synthesize. We present here a facile synthetic route that yields enantiomerically pure derivatives comparable in potency to the parent compounds. Through the generation of truncated variants, we identified a compound with significantly reduced size (MW = 455.5) that nonetheless retains good potency (ki = 78 ± 11 nM) and selectivity for IDE. Notably, the potency of these inhibitors was found to vary as much as 60-fold in a substrate-specific manner, an unexpected finding for active site-directed inhibitors. Collectively, our findings demonstrate that potent, small-molecule IDE inhibitors can be developed that, in certain instances, can be highly substrate selective.
Mapping of the structural gene for the herpes simplex virus type 2 counterpart of herpes simplex virus type 1 glycoprotein C and identification of a type 2 mutant which does not express this glycoprotein (1984)

The gene encoding glycoprotein F (gF) of herpes simplex virus type 2 (HSV-2) was mapped to the region of the viral genome from 0.62 to 0.64 map units. This region is colinear with, and partially homologous to, the region of the HSV-1 genome previously shown to encode gC. Mapping of the gF gene was done by insertion of HSV-2 DNA fragments into the thymidine kinase gene of an HSV-1 virus and screening of the resultant recombinant viruses for the expression of gF. In this way, DNA sequences necessary for the expression of gF in infected cells were also delimited. Because several plaque morphology mutants (syncytial mutants) of HSV-1 have previously been shown to be gC-, a syncytial mutant of HSV-2 (GP) was tested for the expression of gF. It was found to be gF-, indicating that gF is not essential for replication of HSV-2 in cell culture, just as gC is not essential for replication of HSV-1. This result also suggests that the gF- and gC- phenotypes are related in the same, as yet undefined, way to the expression of a syncytial marker. A proposal to change the name of HSV-2 gF to gC (gC-2) is discussed.
The Complete Nucleotide Sequence of a Bovine Enterovirus (1988)

The complete nucleotide sequence of the genome of a bovine enterovirus (strain VG-5-27) has been determined using molecular cloning and DNA sequencing techniques. Excluding the poly(A) tract the genome was 7414 nucleotides long and contained a 5' non-coding region which at 818 nucleotides was longer than that of most picornaviruses. The single large open reading frame encoded a potential polyprotein of 2175 amino acids which showed considerable homology with other enteroviruses. This homology has allowed us to predict the possible cleavage sites of the polyprotein and to identify other features of structural and functional significance which might help us to understand the constraints involved in the evolutionary divergence of these viruses.
Polyethylene glycol and divalent salt-induced DNA reentrant condensation revealed by single molecule measurements (2015)

In this study, we investigated the DNA condensation induced by polyethylene glycol (PEG) with different molecular weights (PEG 600 and PEG 6000) in the presence of NaCl or MgCl2 by using magnetic tweezers (MT) and atomic force microscopy (AFM). The MT measurements show that with increasing NaCl concentration, the critical condensation force in the PEG 600-DNA or PEG 6000-DNA system increased approximately linearly. PEG 6000 solution has a larger critical force than PEG 600 solution at a given NaCl concentration. In comparison, a parabolic trend of the critical condensation force was observed with increasing MgCl2 concentration, indicating that DNA undergoes a reentrant condensation. The AFM results show that the morphologies of the compacted DNA-PEG complexes depended on the salt concentration and were consistent with the MT results.
Gram-negative outer membrane vesicles in vaccine development. (2011)

Gram-negative bacteria naturally and constitutively release lipid bilayer vesicles from the outer membrane. Outer membrane vesicles (OMVs) range in size from approximately 20-200 nanometers in diameter and enclose many native bacterial antigens in the spherical particles. Composed of outer membrane and periplasmic constituents, the vesicles function in diverse roles that, ultimately, make them a transportable part of the bacterial arsenal and survival system. These functional roles entail mediation of bacterial envelope stress, biofilm formation, virulence, and transformation. With their immunogenic properties, self-adjuvanticity, ability to be taken up by mammalian cells, and capacity for enhancement by recombinant engineering, OMVs are attractive candidates for vaccine delivery platforms. The first OMV vaccines were shown to be protective against clonal serogroup B meningococci outbreaks in Cuba, Norway, Brazil, and New Zealand, although there is still no global vaccine against serogroup B meningococci. However, interest in OMVs as vaccine carriers is growing as research exposes more of the molecular intricacies of vesiculation and how the vesicles can be co-opted to fight infectious bacterial agents.
Differential expression of a truncated form of the urokinase-type plasminogen-activator receptor in normal and tumor thyroid cells. (1998)

We studied the urokinase-type plasminogen activator (uPA) receptor (uPA-R) in normal and neoplastic human thyroid cells. It has recently been shown that cleaved forms of uPA-R display an extremely strong chemotactic activity. Normal human thyroid TAD-2 cells express the intact form of the uPA-R and a truncated form lacking the uPA-binding domain on their surface, in a similar manner to tumor thyroid cell lines. However, in tumor thyroid cell lines, the amount of the truncated form is variable: high in papillary carcinoma cells, very low in follicular carcinoma cells, and not detectable in anaplastic carcinoma cells. Similar studies on primary cell cultures confirm the presence of the truncated form of uPA-R in normal and in papillary carcinoma cells and its partial or total loss in follicular carcinoma cells. The presence of truncated uPA-R correlates to uPA secretion, except in papillary carcinoma cells, which express the truncated form of uPA-R but do not release uPA. uPA-R is also able to act as an adhesion receptor by binding vitronectin (VTN) and interacting with integrins. We observe that removal of uPA-R from the surface of normal thyroid and anaplastic carcinoma cells by phosphatidylinositol-specific phospholipase C or treatment with anti-uPA-R antibodies decreases the adhesion of both cell types to VTN and, less efficiently, to fibronectin or collagen. On the other hand, uPA treatment strongly increases the adhesion of anaplastic carcinoma cells specifically to VTN.
Direct counts of aquatic bacteria by a modified epifluorescence technique1 (1975)

Various excitation and emission filters, microscope lamps, membrane filters, and field storage techniques used for direct counting of bacteria by epifluorescence microscopy have been compared. A rapid, simple modification of the Acridine Orange procedure using a new light filter combination, Sartorius cellulose membrane filters, and distilled water rinse gave the brightest cell fluorescence, darkest background, least fading, and highest counts for both estuarine and freshwater samples. Field fixation with Formalin permits storage of bacterial samples for 1 to 2 weeks without changes in bacterial numbers.
Definition of the URL MIME External-Body Access-Type (1996)

This memo defines a new access-type for message/external-body MIME parts for Uniform Resource Locators (URLs). URLs provide schemes to access external objects via a growing number of protocols, including HTTP, Gopher, and TELNET. An initial set of URL schemes are defined in RFC 1738.
Health and population effects of rare gene knockouts in adult humans with related parents (2016)

Examining complete gene knockouts within a viable organism can inform on gene function. We sequenced the exomes of 3222 British adults of Pakistani heritage with high parental relatedness, discovering 1111 rare-variant homozygous genotypes with predicted loss of function (knockouts) in 781 genes. We observed 13.7% fewer homozygous knockout genotypes than we expected, implying an average load of 1.6 recessive-lethal-equivalent loss-of-function (LOF) variants per adult. When genetic data were linked to the individuals' lifelong health records, we observed no significant relationship between gene knockouts and clinical consultation or prescription rate. In this data set, we identified a healthy PRDM9-knockout mother and performed phased genome sequencing on her, her child, and control individuals. Our results show that meiotic recombination sites are localized away from PRDM9-dependent hotspots. Thus, natural LOF variants inform on essential genetic loci and demonstrate PRDM9 redundancy in humans.
Recombinant soluble tumor necrosis factor receptor proteins protect mice from lipopolysaccharide‐induced lethality (1991)

The in vivo efficacy of human recombinant soluble tumor necrosis factor (TNF) receptor protein to prevent and to treat lipopolysaccharide (LPS)-induced lethal toxicity in D-galactosamine-treated mice was investigated. Chimeric proteins of the receptor extracellular domains fused to the hinge region of human IgG3 were expressed in myeloma cells (rsTNFR-h gamma 3). The fusion proteins had a disulfide-bonded dimeric structure. Upon intravenous injection, their serum concentration decreased relatively slowly after an initial phase of rapid elimination. D-galactosamine-sensitized mice were fully protected from the toxic effects of LPS, if the animal were pretreated with rsTNFR-h gamma 3 at 20 micrograms/animal. Partial protection was seen at significantly lower doses and when rsTNFR-h gamma 3 was given up to 3 h after LPS.
Polysilane-Based Polymer Diodes Emitting Ultraviolet Light (1996)

We show for the first time that a thin film of the organic-inorganic hybrid polymer polysilane can be used as an active element in a light-emitting diode with a large active area that generates ultraviolet light at low temperature. The thin-film device emitted 3.35 eV (370 nm) light with moderate efficiency (0.01–0.06%) at temperatures below 210 K. The origin of the emission was assigned to the 1 B u exciton on the one-dimensional silicon chain. The reason for the decrease of the emission efficiency above 50 K was discussed in relation to the order-disorder phase transition in the polysilane thin film.
Drug‐releasing scaffolds fabricated from drug‐loaded microspheres (2001)

Biodegradable scaffolds serve a central role in many strategies for engineering tissue replacements or in guiding tissue regeneration. Typically, these scaffolds function to create and maintain a space and to provide a support for cell adhesion. However, these scaffolds also can serve as vehicles for the delivery of bioactive factors (e.g., protein or DNA) in order to manipulate cellular processes within the scaffold microenvironment. This study presents a novel approach to fabricate tissue-engineering scaffolds capable of sustained drug delivery whereby drug-loaded microspheres are fabricated into structures with controlled porosity. A double-emulsion process was used to fabricate microspheres with encapsulated DNA that retained its integrity and was released from the microspheres within 24 h. These DNA-loaded microspheres subsequently were formed into a nonporous disk or an interconnected open-pore scaffold (>94% porosity) via a gas-foaming process. The disks and scaffolds exhibited sustained plasmid release for at least 21 days and had minimal burst during the initial phase of release. This approach of assembling drug-loaded microspheres into porous and nonporous structures may find great utility in the fabrication of synthetic matrices that direct tissue formation.
Haemodynamic changes during thoracoscopic surgery The effects of one‐lung ventilation compared with carbon dioxide insufflation (2000)

We investigated the haemodynamic and respiratory effects of one-lung ventilation and carbon dioxide insufflation in 13 adult patients undergoing video-assisted thoracoscopy. Cardiorespiratory variables were determined during carbon dioxide insufflation at intrahemithoracic pressures of 5, 10 and 15 mmHg, and after 5 and 15 min of one-lung ventilation. Carbon dioxide insufflation was associated with a clear deterioration in circulatory function. The cardiac index decreased subsequent to increasing intrathoracic pressures. The mean cardiac index (SD) at pressures of 10 and 15 mmHg was 1.86 (0.39) and 1.52 (0.46), respectively, and may be compared with the reduced venous return consistent with tension pneumothorax. One-lung ventilation did not affect haemodynamic variables but reduced arterial oxygenation indices (PaO2/FIO2) from 424.29 (160.79) after induction of anaesthesia, to 207.72 (125.50) after 5 min and 172.04 (72.03) after 15 min of one-lung ventilation, respectively. The oxygenation index was not influenced by intrahemithoracic carbon dioxide insufflation. One-lung ventilation via a double-lumen endobronchial tube is safe and convenient for video-assisted thoracoscopic surgery. It has no further consequences on haemodynamic variables, whereas the compression of the lung by carbon dioxide insufflation may cause circulatory dysfunction.
Probing intermolecular protein–protein interactions in the calcium‐sensing receptor homodimer using bioluminescence resonance energy transfer (BRET) (2002)

The calcium-sensing receptor (CaR) belongs to family C of the G-protein coupled receptor superfamily. The receptor is believed to exist as a homodimer due to covalent and non-covalent interactions between the two amino terminal domains (ATDs). It is well established that agonist binding to family C receptors takes place at the ATD and that this causes the ATD dimer to twist. However, very little is known about the translation of the ATD dimer twist into G-protein coupling to the 7 transmembrane moieties (7TMs) of these receptor dimers. In this study we have attempted to delineate the agonist-induced intermolecular movements in the CaR homodimer using the new bioluminescence resonance energy transfer technique, BRET2, which is based on the transference of energy from Renilla luciferase (Rluc) to the green fluorescent protein mutant GFP2. We tagged CaR with Rluc and GFP2 at different intracellular locations. Stable and highly receptor-specific BRET signals were obtained in tsA cells transfected with Rluc- and GFP2-tagged CaRs under basal conditions, indicating that CaR is constitutively dimerized. However, the signals were not enhanced by the presence of agonist. These results could indicate that at least parts of the two 7TMs of the CaR homodimer are in close proximity in the inactivated state of the receptor and do not move much relative to one another upon agonist activation. However, we cannot exclude the possibility that the BRET technology is unable to register putative conformational changes in the CaR homodimer induced by agonist binding because of the bulk sizes of the Rluc and GFP2 molecules.
Optimal Power Flow Solutions (1968)

A practical method is given for solving the power flow problem with control variables such as real and reactive power and transformer ratios automatically adjusted to minimize instantaneous costs or losses. The solution is feasible with respect to constraints on control variables and dependent variables such as load voltages, reactive sources, and tie line power angles. The method is based on power flow solution by Newton's method, a gradient adjustment algorithm for obtaining the minimum and penalty functions to account for dependent constraints. A test program solves problems of 500 nodes. Only a small extension of the power flow program is required to implement the method.
Comparative Studies of Glycosaminoglycan Involvement inChlamydia pneumoniaeandC. trachomatisInvasion of Host Cells (2003)

The role of glycosaminoglycans (GAGs) in the invasion of host cells by Chlamydia pneumoniae strains TW-183 and A-03 was investigated and compared with the role of invasion by C. trachomatis serovars L2 and E. The quantities of epithelial and endothelial cell-surface GAGs, as well as chlamydial elementary body (EB)-surface GAGs, were investigated. When specific enzymes were used to cleave GAGs from host cells or EBs, decreased infection rates were observed with C. pneumoniae and C. trachomatis serovar L2 in epithelial cells, but not in endothelial cells. Larger decreases in infection occurred with enzyme-treated EBs in GAG-deficient Chinese hamster ovary (CHO) cells. EBs grown in GAG-deficient CHO cells resulted in lower amounts of EB surface GAGs and decreased infectivity of epithelial cells. The results indicate that C. pneumoniae and C. trachomatis L2 EB-surface GAGs and host cell-surface GAGs are involved in invasion of bronchial epithelial cells but not of human umbilical vein endothelial cells.
Simultaneous detection of Escherichia coli O157∶H7 and Salmonella Typhimurium using quantum dots as fluorescence labels (2005)

In this study, we explored the use of semiconductor quantum dots (QDs) as fluorescence labels in immunoassays for simultaneous detection of two species of foodborne pathogenic bacteria, Escherichia coli O157:H7 and Salmonella Typhimurium. QDs with different sizes can be excited with a single wavelength of light, resulting in different emission peaks that can be measured simultaneously. Highly fluorescent semiconductor quantum dots with different emission wavelengths (525 nm and 705 nm) were conjugated to anti-E. coli O157 and anti-Salmonella antibodies, respectively. Target bacteria were separated from samples by using specific antibody coated magnetic beads. The bead-cell complexes reacted with QD-antibody conjugates to form bead-cell-QD complexes. Fluorescent microscopic images of QD labeled E. coli and Salmonella cells demonstrated that QD-antibody conjugates could evenly and completely attach to the surface of bacterial cells, indicating that the conjugated QD molecules still retain their effective fluorescence, while the conjugated antibody molecules remain active and are able to recognize their specific target bacteria in a complex mixture. The intensities of fluorescence emission peaks at 525 nm and 705 nm of the final complexes were measured for quantitative detection of E. coli O157:H7 and S. Typhimurium simultaneously. The fluorescence intensity (FI) as a function of cell number (N) was found for Salmonella and E. coli, respectively. The regression models can be expressed as: FI = 60.6 log N- 250.9 with R(2) = 0.97 for S. Typhimurium, and FI = 77.8 log N- 245.2 with R(2) = 0.91 for E. coli O157:H7 in the range of cell numbers from 10(4) to 10(7) cfu ml(-1). The detection limit of this method was 10(4) cfu ml(-1). The detection could be completed within 2 hours. The principle of this method could be extended to detect multiple species of bacteria (3-4 species) simultaneously, depending on the availability of each type of QD-antibody conjugates with a unique emission peak and the antibody coated magnetic beads specific to each species of bacteria.
An Alteration in the Structure of the Minor Groove of Duplex DNA Induced by the Formation of an Intermolecular d(GA)n:d(GA)n ·d(TC)n Triplex (1997)

A simple homopolymeric purine:purine.pyrimidine, d(GA)n:d(GA)n.d(TC)n, triplex DNA was generated in the presence of magnesium ion at neutral pH. Hydrogen bonding of the N7 positions of guanines and adenines was investigated by 7-deaza base substitutions and protection from chemical modification by dimethyl sulfate (DMS). Chemical modification of this triplex with DMS revealed an unexpected triplex specific hypermodification in the N3 positions of the adenines in addition to the protection in the N7 positions of the guanines. The significance of this increase in the chemical accessibility of the N3 positions of adenines in the minor groove and possible relevance of dehydration to the mechanism of triplex formation and stability is discussed.
Higher Inflammatory Marker Levels in Older Persons: Associations With 5-Year Change in Muscle Mass and Muscle Strength (2009)

TNF-alpha and its soluble receptors showed the most consistent associations with decline in muscle mass and strength. The results suggest a weight-associated pathway for inflammation in sarcopenia.
A generalized processor sharing approach to flow control in integrated services networks: the single-node case (1993)

The problem of allocating network resources to the users of an integrated services network is investigated in the context of rate-based flow control. The network is assumed to be a virtual circuit, connection-based packet network. It is shown that the use of generalized processor sharing (GPS), when combined with leaky bucket admission control, allows the network to make a wide range of worst-case performance guarantees on throughput and delay. The scheme is flexible in that different users may be given widely different performance guarantees and is efficient in that each of the servers is work conserving. The authors present a practical packet-by-packet service discipline, PGPS that closely approximates GPS. This allows them to relate results for GPS to the packet-by-packet scheme in a precise manner. The performance of a single-server GPS system is analyzed exactly from the standpoint of worst-case packet delay and burstiness when the sources are constrained by leaky buckets. The worst-case session backlogs are also determined.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>