gebhart/patrepeval huggingface dataset:
Mislocalization of XPF-ERCC1 Nuclease Contributes to Reduced DNA Repair in XP-F Patients (2010)

Xeroderma pigmentosum (XP) is caused by defects in the nucleotide excision repair (NER) pathway. NER removes helix-distorting DNA lesions, such as UV-induced photodimers, from the genome. Patients suffering from XP exhibit exquisite sun sensitivity, high incidence of skin cancer, and in some cases neurodegeneration. The severity of XP varies tremendously depending upon which NER gene is mutated and how severely the mutation affects DNA repair capacity. XPF-ERCC1 is a structure-specific endonuclease essential for incising the damaged strand of DNA in NER. Missense mutations in XPF can result not only in XP, but also XPF-ERCC1 (XFE) progeroid syndrome, a disease of accelerated aging. In an attempt to determine how mutations in XPF can lead to such diverse symptoms, the effects of a progeria-causing mutation (XPF(R153P)) were compared to an XP-causing mutation (XPF(R799W)) in vitro and in vivo. Recombinant XPF harboring either mutation was purified in a complex with ERCC1 and tested for its ability to incise a stem-loop structure in vitro. Both mutant complexes nicked the substrate indicating that neither mutation obviates catalytic activity of the nuclease. Surprisingly, differential immunostaining and fractionation of cells from an XFE progeroid patient revealed that XPF-ERCC1 is abundant in the cytoplasm. This was confirmed by fluorescent detection of XPF(R153P)-YFP expressed in Xpf mutant cells. In addition, microinjection of XPF(R153P)-ERCC1 into the nucleus of XPF-deficient human cells restored nucleotide excision repair of UV-induced DNA damage. Intriguingly, in all XPF mutant cell lines examined, XPF-ERCC1 was detected in the cytoplasm of a fraction of cells. This demonstrates that at least part of the DNA repair defect and symptoms associated with mutations in XPF are due to mislocalization of XPF-ERCC1 into the cytoplasm of cells, likely due to protein misfolding. Analysis of these patient cells therefore reveals a novel mechanism to potentially regulate a cell's capacity for DNA repair: by manipulating nuclear localization of XPF-ERCC1.
Relationship of MRI Delayed Contrast Enhancement to Irreversible Injury, Infarct Age, and Contractile Function (1999)

In the pathophysiologies investigated, contrast MRI distinguishes between reversible and irreversible ischemic injury independent of wall motion and infarct age.
Photoprotective compounds from marine organisms (2010)

The substantial loss in the stratospheric ozone layer and consequent increase in solar ultraviolet radiation on the earth's surface have augmented the interest in searching for natural photoprotective compounds in organisms of marine as well as freshwater ecosystems. A number of photoprotective compounds such as mycosporine-like amino acids (MAAs), scytonemin, carotenoids and several other UV-absorbing substances of unknown chemical structure have been identified from different organisms. MAAs form the most common class of UV-absorbing compounds known to occur widely in various marine organisms; however, several compounds having UV-screening properties still need to be identified. The synthesis of scytonemin, a predominant UV-A-photoprotective pigment, is exclusively reported in cyanobacteria. Carotenoids are important components of the photosynthetic apparatus that serve both light-harvesting and photoprotective functions, either by direct quenching of the singlet oxygen or other toxic reactive oxygen species or by dissipating the excess energy in the photosynthetic apparatus. The production of photoprotective compounds is affected by several environmental factors such as different wavelengths of UVR, desiccation, nutrients, salt concentration, light as well as dark period, and still there is controversy about the biosynthesis of various photoprotective compounds. Recent studies have focused on marine organisms as a source of natural bioactive molecules having a photoprotective role, their biosynthesis and commercial application. However, there is a need for extensive work to explore the photoprotective role of various UV-absorbing compounds from marine habitats so that a range of biotechnological and pharmaceutical applications can be found.
Chlamydial infection. Results of micro-immunofluorescence tests for the detection of type-specific antibody in certain chlamydial infections. (1972)

The development of the micro-immunofluorescence (micro-IF) typing test by Wang and Grayston
A microfluidic platform for complete mammalian cell culture (2010)

We introduce the first lab-on-a-chip platform for complete mammalian cell culture. The new method is powered by digital microfluidics (DMF), a technique in which nanolitre-sized droplets are manipulated on an open surface of an array of electrodes. This is the first application of DMF to adherent cell culture and analysis, and more importantly, represents the first microfluidic platform capable of implementing all of the steps required for mammalian cell culture-cell seeding, growth, detachment, and re-seeding on a fresh surface. Three key innovations were required to implement complete cell culture on a microfluidic device: (1) a technique for growing cells on patterned islands (or "adhesion pads") positioned on an array of DMF actuation electrodes; (2) a method for rapidly and efficiently exchanging media and other reagents on cells grown on adhesion pads; and (3) a system capable of detachment and collection of cells from an (old) origin site and delivery to a (new) destination site for subculture. The new technique was applied to cells from several different lines which were seeded and repeatedly subcultured for weeks at a time in 150 nL droplets. Cells handled in this manner exhibited growth characteristics and morphology comparable to those cultured in standard tissue culture vessels. To illustrate an application for this system, a microfluidic method was developed to implement transient transfection-we propose that the combination of this technique with multigenerational culture allows for "on-demand" generation of transiently transfected cells. Broadly, we anticipate that the automated cell microculture technique presented here will be useful in myriad applications that would benefit from automated mammalian cell culture.
Protecting information on the Web (2000)

The World Wide Web is giving rise to a new type of distributed information system, one with an Internet (or intranet) communication platform, a broader client/server architecture, the entire population of Internet users as potential clients, and all available Web servers as potential servers. This new generation of global information systems has eliminated many technological barriers to free circulation of information, allowing for development of public utility services such as the ACM Digital Library [1]. Businesses are embracing intranet and Web technology for internal communication, integration of dispersed branches and points-of-sale, and provision of new customer services.
Anti-Endotoxin Monoclonal Antibodies (1992)

Several monoclonal antibodies directed against bacterial lipopolysaccharide (endotoxin) are being developed for the adjunctive treatment of gram-negative sepsis. Two of these, E5 (XOMA, Berkeley, Calif.)1 and HA-1A (Centocor, Malvern, Pa.),2 have been studied in clinical trials and evaluated by the Food and Drug Administration for use in the United States. An open advisory-committee meeting was held by the FDA on September 4, 1991, at which new information was presented about the preclinical and clinical studies of these two products.3 This article discusses some of the issues relating to the development and evaluation of these agents in the context of this . . .
A Comprehensive Mathematical Model for Three-Body Binding Equilibria (2013)

Three-component systems are often more complex than their two-component counterparts. Although the reversible association of three components in solution is critical for a vast array of chemical and biological processes, no general physical picture of such systems has emerged. Here we have developed a general, comprehensive framework for understanding ternary complex equilibria, which relates directly to familiar concepts such as EC50 and IC50 from simpler (binary complex) equilibria. Importantly, application of our model to data from the published literature has enabled us to achieve new insights into complex systems ranging from coagulation to therapeutic dosing regimens for monoclonal antibodies. We also provide an Excel spreadsheet to assist readers in both conceptualizing and applying our models. Overall, our analysis has the potential to render complex three-component systems--which have previously been characterized as "analytically intractable"--readily comprehensible to theoreticians and experimentalists alike.
Basic Principles of the CIP‐System and Proposals for a Revision (1982)

Abstract “From Configurational Notation of Stereoisomers to the Conceptual Basis of Stereochemistry” is the title of a lecture [V. Prelog, ACS Symp. Ser. No. 12 (1975) 179] in which the chronologically and alphabetically third member of the CIP‐triumvirate discusses the history of the CIP‐system. The experience accumulated in the meantime, particularly the efforts to teach computers to use the system as described in 1966 by Cahn, Ingold and Prelog, has shown that certain of its aspects must be more strictly formulated and others modified. Questions dealing with stereoisomers (and stereotopicity), which previously have been treated predominantly in a pragmatic manner, are now discussed in a systematic way.
Reactive oxygen species inducible by low-intensity laser irradiation alter DNA synthesis in the haemopoietic cell line U937 (1996)

These findings demonstrate that laser-inducible ROS can mediate laser's effects on this cell line.
Three-dimensional structure of recombinant human interferon-gamma (1991)

The x-ray crystal structure of recombinant human interferon-gamma has been determined with the use of multiple-isomorphous-replacement techniques. Interferon-gamma, which is dimeric in solution, crystallizes with two dimers related by a noncrystallographic twofold axis in the asymmetric unit. The protein is primarily alpha helical, with six helices in each subunit that comprise approximately 62 percent of the structure; there is no beta sheet. The dimeric structure of human interferon-gamma is stabilized by the intertwining of helices across the subunit interface with multiple intersubunit interactions.
Digital spread-spectrum multipath-diversity receiver for indoor communications (2003)

The design and performance measurements of a digital direct-sequence spread-spectrum (DS-SS) receiver for a wireless indoor communication system are provided. The system operates at a chip rate of 16.368*10/sup 6/ chips/s with a processing gain of 30 dB. A RAKE-structure is used to resolve the time diversity due to multipath propagation. The received signal is despread in eight arms at the baseband using a digital time-integrating correlator. All algorithms for synchronization and data demodulation are implemented as software modules on a general-purpose digital signal processor (DSP). The authors give a derivation of these digital algorithms, a description of the hardware implementation, and results of the first measurements.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
In vivo gene delivery. Efficient transfection of T lymphocytes in adult mice (1993)

We have demonstrated that a single intraperitoneal injection of cationic liposomes complexed to a chloramphenicol acetyltransferase (CAT) gene expression plasmid can transfect the majority of splenic Thy 1.2+ T lymphocytes, as well as significant numbers of bone marrow-derived hematopoietic cells, in adult mice. CAT activity was detected in the spleen for at least 2 weeks, and there was no evidence of treatment-related toxicity. Some degree of tissue-specific transgene expression was achieved by varying the cationic lipid used.
Microfluidic filtration system to isolate extracellular vesicles from blood (2012)

Extracellular vesicles are released by various cell types, particularly tumor cells, and may be potential targets for blood-based cancer diagnosis. However, studies performed on blood-borne vesicles to date have been limited by lack of effective, standardized purification strategies. Using in situ prepared nanoporous membranes, we present a simple strategy employing a microfluidic filtration system to isolate vesicles from whole blood samples. This method can be applied to purify nano-sized particles from blood allowing isolation of intact extracellular vesicles, avoiding the need for laborious and potentially damaging centrifugation steps or overly specific antibody-based affinity purification. Porous polymer monoliths were integrated as membranes into poly(methyl methacrylate) microfluidic chips by benchtop UV photopolymerization through a mask, allowing precise positioning of membrane elements while preserving simplicity of device preparation. Pore size could be manipulated by changing the ratio of porogenic solvent to prepolymer solution, and was tuned to a size proper for extraction of vesicles. Using the membrane as a size exclusion filter, we separated vesicles from cells and large debris by injecting whole blood under pressure through the microfluidic device. To enhance isolation purity, DC electrophoresis was employed as an alternative driving force to propel particles across the filter and increase the separation efficiency of vesicles from proteins. From the whole blood of melanoma-grown mice, we isolated extracellular vesicles and performed RT-PCR to verify their contents of RNA. Melan A mRNA derived from melanoma tumor cells were found enriched in filtered samples, confirming the recovery of vesicles via their cargo. This filtration system can be incorporated into other on-chip processes enabling integrated sample preparation for the downstream analysis of blood-based extracellular vesicles.
Immunostimulatory human urinary protein. (1992)

We have previously extracted a protein from inflammatory mouse granuloma that fully protects normal mice against lethal Listeria monocytogenes infection. We now report that polyclonal antibodies directed against this protein react with a human urinary fraction that also provides full protection of normal mice against L. monocytogenes. Murine monoclonal antibodies completely inhibit the protective activity of the human urinary fraction. We have purified to apparent homogeneity a human glycoprotein of 43 kDa (HGP.43), pI = 3.2 +/- 0.2. HGP.43 injected i.v. at 250 micrograms/kg fully protected mice against a lethal inoculum of L. monocytogenes. Such resistance followed injection of HGP.43, 4 days before and, still significantly, 8 hr after Listeria infection. In scid mice lacking T and B cells, similar resistance to L. monocytogenes was observed. Inflammatory murine macrophages became cytostatic against Lewis carcinoma cells after incubation with 1.5 nM HGP-43.
Virulence factors of the coagulase-negative staphylococci (2004)

Coagulase-negative staphylococci (CNS) have gained substantial interest as pathogens involved in nosocomial, particularly catheter-related infections. The pathogenic potential of CNS is mainly due to their capacity to form biofilms on indwelling medical devices. In a biofilm, the bacteria are protected against antibiotics and from attacks by the immune system. The factors contributing to biofilm formation are among the best-studied virulence factors of CNS and comprise factors involved in the adhesion to a catheter surface and in cell accumulation. CNS usually persist in the host in relative silence, but may cause sepsis, for which the recently found inflammatory peptides called phenol-soluble modulins are prime candidates. Many CNS also produce several lipases, proteases, and other exoenzymes, which possibly contribute to the persistence of CNS in the host and may degrade host tissue. We are also beginning to understand how regulators of virulence trigger the expression of virulence factors in CNS. A better conception of the mechanisms underlying the pathogenicity and the frequently encountered antibiotic resistance of CNS may help to develop novel, efficient anti-staphylococcal therapeutics.
Analysis of the agrotis segetum pheromone gland transcriptome in the light of Sex pheromone biosynthesis (2015)

The massive sequencing technology generates enormous amounts of candidate genes potentially involved in pheromone biosynthesis but testing their function by heterologous expression or gene silencing is a bottleneck. We confirmed the function of a previously identified desaturase gene and a fatty-acyl reductase gene by heterologous expression, but the acetyltransferase postulated to be involved in pheromone biosynthesis remains illusive, in spite of 34 candidates being assayed. We also generated lists of gene candidates that may be useful for characterizing the acetyl-CoA carboxylase, fatty acid synthetase and β-oxidation enzymes.
Fibronectin mRNA Splice Variant in Articular Cartilage Lacks Bases Encoding the V, III-15, and I-10 Protein Segments (1996)

Fibronectin is an extracellular matrix glycoprotein encoded by a single gene. Alternative RNA splicing has been reported at three sites, ED (extra type III domain)-A, ED-B, and the variable or V region. Articular cartilage fibronectin monomers are rarely (ED-A)+, but approximately 25% are (ED-B)+. RNA gel electrophoresis and Northern blot analysis identified two (ED-B)+ and two (ED-B)- fibronectin transcripts in cartilage, each pair differing by approximately 750 bases. This difference results from a previously unreported RNA splicing pattern that eliminates not only the V region but also nucleotides encoding protein segments III-15 and I-10. This new splice variant, which we designate (V+C)-, represents the majority of fibronectin transcripts in equine, canine, and rabbit articular cartilage but is absent in the liver. Reverse transcriptase-polymerase chain reaction analyses of 11 additional equine tissues failed to detect the (V+C)- splice variant, except for very low levels in lymph node, bone, aorta, and skin. Furthermore, chondrocytes grown in monolayer culture maintain high levels of fibronectin expression but stop expressing (V+C)- transcripts over time. The tissue-specific expression pattern of this novel fibronectin isoform suggests that it may have an important function in the matrix organization of cartilage.
Phase-controlled integrated photonic quantum circuits (2009)

Scalable photonic quantum technologies are based on multiple nested interferometers. To realize this architecture, integrated optical structures are needed to ensure stable, controllable, and repeatable operation. Here we show a key proof-of-principle demonstration of an externallycontrolled photonic quantum circuit based upon UV-written waveguide technology. In particular, we present non-classical interference of photon pairs in a Mach-Zehnder interferometer constructed with X couplers in an integrated optical circuit with a thermo-optic phase shifter in one of the interferometer arms.
Phase II Trial of a Single Weekly Intravenous Dose of Ranpirnase in Patients With Unresectable Malignant Mesothelioma (2002)

PURPOSE: A multicenter phase II trial of ranpirnase (Onconase; Alfacell Corp, Bloomfield, NJ) as a single agent was conducted to further assess the safety and clinical efficacy of this novel antitumor ribonuclease. Patients with unresectable and histologically confirmed malignant mesothelioma (MM) were eligible. PATIENTS AND METHODS: One hundred five patients with Eastern Cooperative Oncology Group performance status 0 to 2 were enrolled onto the study. Thirty-seven percent of patients had not responded to prior chemotherapy. The primary end point of the study was survival. Tumor responses and time to progression were also assessed. The Cancer and Leukemia Group B (CALGB) prognostic group criteria were used to define a treatment target group (TTG). Both the intent-to-treat (ITT) and the TTG populations were analyzed for survival. RESULTS: Median survival times of 6 months for the ITT and 8.3 months for the TTG populations were observed. The 1- and 2-year survival rates were 34.3% and 21.6% for ITT, respectively, and 42% and 26.8% for TTG, respectively. Among the 81 patients assessable for tumor response, four had partial responses, two had minor regressions, and thirty-five experienced stabilization of previously progressive disease. Patients with responses and stable disease demonstrated markedly prolonged survival. Ranpirnase was well tolerated in the majority of patients, and there were no drug-related deaths. CONCLUSION: Ranpirnase demonstrated activity and a tolerable toxicity profile in patients with unresectable MM. The prognostic value of the CALGB groups was confirmed.
New dibenzothiadiazepine derivatives with antidepressant activities (1991)

A new series of 11-[(aminoalkyl)carbonyl] derivatives of 6,11-dihydrodibenzo[c,f][1,2,5]thiadiazepine 5,5-dioxide (10-39) were synthesized and evaluated for potential antidepressant activity in the apomorphine-induced hypothermia (Apo 16) test. Effects on reserpine-induced hypothermia and toxicity for the most potent antagonists of Apo 16 hypothermia were also studied. Structure-activity relationships are reported. Anticholinergic effects were evaluated for compound 12, identified as the most potent and least toxic in this series, by assessing physostigmine lethality. Compound 12 was also subjected to X-ray analysis.
Idiopathic Epilepsy and Paroxysmal Dyskinesia (2001)

Although some motor manifestations of epilepsy and of paroxysmal dyskinesia may be difficult to differentiate clinically, the current understanding is that the two disorders are clinically distinct. However, there are several recent reports of families in which different individuals had either disorder or both manifestations, with age-related expression. Co-occurrence makes it likely that a common, genetically determined, pathophysiologic abnormality is variably expressed in the cerebral cortex and in basal ganglia. A rather homogeneous syndrome of autosomal dominant infantile convulsions and paroxysmal (dystonic) choreoathetosis (ICCA) was described in six families from France, China and Japan. Linkage analysis in the French and Chinese families allowed the mapping of the disease gene in a 10-cM interval within the pericentromeric region of chromosome 16. An Italian pedigree in which three members in the same generation were affected by rolandic epilepsy, paroxysmal exercise-induced dystonia (PED), and writer's cramp was subsequently reported. Linkage analysis showed a common homozygous haplotype in a critical region spanning 6 cM and entirely included within the ICCA critical region. Clinical analogies and linkage findings suggest that the same gene could be responsible for rolandic epilepsy, PED, writer's cramp (WC), and ICCA, with specific mutations accounting for each of these mendelian disorders. Evidence for a major gene or a cluster of genes for epilepsy and paroxysmal dyskinesia to the pericentromeric region of chromosome 16 is reinforced by the recent linkage of a family with autosomal dominant paroxysmal dyskinesia to a critical region partially overlapping with ICCA and contiguous to the RE-PED-WC regions. Additional autosomal dominant pedigrees are on record, from Australia and Italy, in which epilepsy was variably associated with paroxysmal kinesigenic or exercise-induced dystonia. Ion channel genes are potentially interesting candidates for syndromes featuring both these paroxysmal neurologic disorders. Increased awareness of their possible co-occurrence will certainly increase the number of observations in the next few years.