gebhart/patrepeval huggingface dataset:
Synthesis and physicochemical and immunological characterization of pneumococcus type 12F polysaccharide-diphtheria toxoid conjugates (1988)

A scheme for the synthesis and purification of conjugates, composed of the type 12F capsular polysaccharide of Streptococcus pneumoniae (Pn12F) and diphtheria toxoid, is described. The scheme is a modification of that described previously for the Vi capsular polysaccharide of Salmonella typhi, a linear homopolymer of N-acetylgalactoseaminouronic acid (S. C. Szu, A. L. Stone, J. D. Robbins, R. Schneerson, and J. B. Robbins, J. Exp. Med. 166:1510-1524, 1986). Pn12F is a branched-chain copolymer composed of a hexasaccharide repeating unit containing an aminouronic acid, N-acetylmannoseaminouronic acid (K. Leontein, B. Lindberg, and J. Lonngren, Can. J. Chem. 59:2081-2085, 1981). Sulfhydryl groups were introduced into Pn12F by forming an amide bond between cystamine and carboxyl groups of N-acetylmannoseaminouronic acid in the presence of a carbodiimide. The disulfide moiety of cystamine was reduced to form the cysteamine derivative of Pn12F which was, in turn, covalently bound to diphtheria toxoid by using the heterobifunctional linker N-succinimidyl-3-(2-pyridylthio)propionate. Unbound, high-molecular-weight Pn12F was removed from the conjugate by hydrophobic interaction chromatography through octyl Sepharose by using n-octyl-beta-D-glucopyranoside as the eluent. In young outbred mice, Pn12F did not elicit detectable serum antibodies. Pn12F-diphtheria toxoid, in contrast, elicited antibodies after two injections and had T-cell-dependent properties as evidenced by a response to priming and by its ability to elicit booster responses. This scheme seems applicable to the synthesis of conjugates with other capsular polysaccharides containing aminouronic acids. Clinical evaluation of Pn12F-diphtheria toxoid conjugates in healthy and in immunocompromised hosts is planned.
Software Implemented Fault Tolerance: Technologies and Experience (1993)

By software implemented fault tolerance, we mean a set of software facilities to detect ‘and recover from faults that are are not handled by the underlying hardware or operating system. We consider those faults that cause an application process to crash or hang; they include software faults as well as faults in the underlying hardware and operating system layers if they are undetected in those layers. We define 4 levels of software fault tolerance based on availability and data consistency of an application in the presence of such faults. Watchd, libft and nDFS are reusable components that provide up to the 3rd level of software fault tolerance. They perform, respectively, automatic detection and restart of failed processes, periodic checkpointing and recovery of critical volatile data, and replication and synchronization of persistent data in an application software system. These modules have been ported to a number of UNIX’ platforms and can be used by any application with minimal programming egort. Some newer telecommunications products in AT&T have already enhanced their fault-tolerance capability using these three components. Experience with those products to date indicates that these modules provide eficient and economical means to increase the level of fault tolerance in a software product. The performance overhead due to these components depends on the level and varies from 0.1% to 14% based on the amount of critical data being checkpointed and replicated.
Biologically Active Thiazolidinone (1978)

Department of Pharmacology and Therapeutics, King George's Medical College, Lucknow, India <em>Manuscript received 30 September 1971, revised 6 March 1978 accepted 13 April 1978</em> Some new thiazolidinone derivatives with an aromatic nitrogen hetrocyclic nucleus as possible amoebicldal, cysticidal and fungicldal agents have been synthesized. They have been also screened for anticonvulsant activity.
Removable and Recyclable Conjugated Polymers for Highly Selective and High-Yield Dispersion and Release of Low-Cost Carbon Nanotubes (2016)

High-purity semiconducting single-walled carbon nanotubes (s-SWNTs) with little contamination are desired for high-performance electronic devices. Although conjugated polymer wrapping has been demonstrated as a powerful and scalable strategy for enriching s-SWNTs, this approach suffers from significant contaminations by polymer residues and high cost of conjugated polymers. Here, we present a simple but general approach using removable and recoverable conjugated polymers for separating s-SWNTs with little polymer contamination. A conjugated polymer with imine linkages was synthesized to demonstrate this concept. Moreover, the SWNTs used are without prepurifications and very low cost. The polymer exhibits strong dispersion for large-diameter s-SWNTs with high yield (23.7%) and high selectivity (99.7%). After s-SWNT separation, the polymer can be depolymerized into monomers and be cleanly removed under mild acidic conditions, yielding polymer-free s-SWNTs. The monomers can be almost quantitatively recovered to resynthesize polymer. This approach enables isolation of "clean" s-SWNTs and, at the same time, greatly lowers costs for SWNT separation.
Inhibition of the DNA‐binding activity of NF‐κB by gold compounds in vitro (1995)

Nuclear factor kappa B (NF-kappa B) is a transcription factor that is critical for the inducible expression of multiple cellular and viral genes. DNA binding activity is essential for its function. Here, we report that gold compounds, especially aurothioglucose (AuTG), have a strong inhibitory effect on NF-kappa B-DNA binding. Our finding also reveals that Zn2+ is a necessary component of NF-kappa B for its DNA binding activity and that gold ion can efficiently block NF-kappa B-DNA binding, presumably through oxidation of the cysteins associated with zinc. This redox mechanism may provide an explanation for the observed efficacy of gold compounds in the treatment of rheumatoid arthritis.
Expression of an Exogenous Growth Hormone Gene by Transplantable Human Epidermal Cells (1987)

Retrovirus-mediated gene transfer was used to introduce a recombinant human growth hormone gene into cultured human keratinocytes. The transduced keratinocytes secreted biologically active growth hormone into the culture medium. When grafted as an epithelial sheet onto athymic mice, these cultured keratinocytes reconstituted an epidermis that was similar in appearance to that resulting from normal cells, but from which human growth hormone could be extracted. Transduced epidermal cells may prove to be a general vehicle for the delivery of gene products by means of grafting.
The use of glatiramer acetate in the treatment of multiple sclerosis. (2006)

Glatiramer acetate is a collection of synthetic polypeptides indicated as therapy for relapsing a remitting multiple sclerosis (MS). Current understanding of the immunological and neuroprotective mechanisms of action of GA makes it unique among current MS therapies. The clinical efficacy of GA appears similar to that of the recombinant beta interferons. GA has a favorable side effect profile with excellent patient compliance and long-term acceptance. The results of pivotal controlled clinical trials and long-term data derived from organized extension studies are reviewed. Supportive data from open-label comparison, combination treatment and therapeutic switch studies are also provided to enable informed decisions on the appropriate place for GA among other immunomodulatory treatments for relapsing MS.
Protein purification using chromatography: selection of type, modelling and optimization of operating conditions (2008)

To achieve a high level of purity in the purification of recombinant proteins for therapeutic or analytical application, it is necessary to use several chromatographic steps. There is a range of techniques available including anion and cation exchange, which can be carried out at different pHs, hydrophobic interaction chromatography, gel filtration and affinity chromatography. In the case of a complex mixture of partially unknown proteins or a clarified cell extract, there are many different routes one can take in order to choose the minimum and most efficient number of purification steps to achieve a desired level of purity (e.g. 98%, 99.5% or 99.9%). This review shows how an initial 'proteomic' characterization of the complex mixture of target protein and protein contaminants can be used to select the most efficient chromatographic separation steps in order to achieve a specific level of purity with a minimum number of steps. The chosen methodology was implemented in a computer- based Expert System. Two algorithms were developed, the first algorithm was used to select the most efficient purification method to separate a protein from its contaminants based on the physicochemical properties of the protein product and the protein contaminants and the second algorithm was used to predict the number and concentration of contaminants after each separation as well as protein product purity. The application of the Expert System approach was experimentally tested and validated with a mixture of four proteins and the experimental validation was also carried out with a supernatant of Bacillus subtilis producing a recombinant beta-1,3-glucanase. Once the type of chromatography is chosen, optimization of the operating conditions is essential. Chromatographic elution curves for a three-protein mixture (alpha-lactoalbumin, ovalbumin and beta-lactoglobulin), carried out under different flow rates and ionic strength conditions, were simulated using two different mathematical models. These models were the Plate Model and the more fundamentally based Rate Model. Simulated elution curves were compared with experimental data not used for parameter identification. Deviation between experimental data and the simulated curves using the Plate Model was less than 0.0189 (absorbance units); a slightly higher deviation [0.0252 (absorbance units)] was obtained when the Rate Model was used. In order to optimize operating conditions, a cost function was built that included the effect of the different production stages, namely fermentation, purification and concentration. This cost function was also successfully used for the determination of the fraction of product to be collected (peak cutting) in chromatography. It can be used for protein products with different characteristics and qualities, such as purity and yield, by choosing the appropriate parameters.
Monte Carlo simulation of expected outcomes with the AcrySof®toric intraocular lens (2008)

Monte Carlo simulation suggests that surgical variability and lens orientation/rotation variability may combine to produce small reductions in the correction achieved with the AcrySof Toric IOL. Adopting more aggressive lens selection criteria may yield significantly lower residual astigmatism values for many patients, with negligible overcorrections. Surgeons are encouraged to evaluate their AcrySof Toric outcomes to determine if they should modify their individual lens selection criteria, or their default surgically induced astigmatism value, to benefit their patients.
Plasma kinins in synovial exudates. (1970)

Kinin levels equivalent to 1-30 × 10(-9) m bradykinin were found in 33 out of 82 exudates from rheumatoid joints. Only 2 of 27 fluids from joint effusions caused by osteoarthrosis or trauma, contained detectable levels of kinin (1-5 × 10(-9) m bradykinin). The kinin concentrations showed little or no correlation with the white blood cell counts, protein concentrations and lactate dehydrogenase and acid phosphatase activities, in synovial fluids. Data on the pain felt in joints suggested that in higher concentrations kinins contribute to arthritic pain, but that other pain-producing factors are undoubtedly involved.
Proton and nitrogen sequential assignments and secondary structure determination of the human FK506 and rapamycin binding protein (1991)

Sequential 1H and 15N assignments of human FKBP, a cytosolic binding protein for the immunosuppressive agents FK506 and rapamycin, are reported. A combination of homonuclear and relayed heteronuclear experiments has enabled assignment of 98 of 99 backbone amide NHs, 119 of 120 C alpha Hs, 97 of 99 non-proline amide 15Ns, and 375 of 412 side-chain resonances of this 107-residue protein. Long-range NOEs are used to demonstrate that FKBP has a novel folding topology consisting of a five-stranded antiparallel beta sheet with +3, +1, -3, +1 loop connectivity.
Lactobacilli Expressing Variable Domain of Llama Heavy‐Chain Antibody Fragments (Lactobodies) Confer Protection against Rotavirus‐Induced Diarrhea (2006)

Transformed lactobacilli may form the basis of a novel form of prophylactic treatment against rotavirus infections and other diarrheal diseases.
Putative Role of Adhesion Molecules in Metabolic Disorders (1997)

Diabetes mellitus is associated with an increased risk of premature vascular disease. Vascular research is focusing on a potential role of adhesion molecules in diabetes mellitus, since classical risk factors including hyperlipidemia and hypertension do not completely account for the increased incidence of atherosclerosis in diabetes. After the expression of adhesion molecules on the cell surface, they are shed into plasma. Thus plasma concentrations of circulating adhesion molecules may be representative for endothelial activation, damage or turnover. Recently, evidence has been accumulating that increased plasma levels of adhesion molecules may predict cardiovascular disease, may be pathognomonic for diabetic microangiopathy or may even play a functional pathophysiologic role. The purpose of this article is to briefly summarise the role of (circulating) adhesion molecules in diabetes mellitus.
埃德蒙德·胡塞尔的“私人札记” (2009)

1906—1908年是胡塞尔思想发展的重要年代，是他从描述心理学走向超越论现象学的过渡时期。在此期间他曾于一个笔记本中做过一些私人的、类似日记的札记，其中最主要的内容是他对以往思想的回顾和清算，以及他对未来工作的构想与计划。这些计划后来大都得到了实施。除此之外，胡塞尔在里面还留有一些内心的独白，表露出他在此期间的复杂心态。这份文献提供了理解胡塞尔哲学思想和哲学人格的重要依据。
Chromatin Profiling Reveals Regulatory Network Shifts and a Protective Role for Hepatocyte Nuclear Factor 4α during Colitis (2014)

Transcriptional regulatory mechanisms likely contribute to the etiology of inflammatory bowel disease (IBD), as genetic variants associated with the disease are disproportionately found at regulatory elements. However, the transcription factors regulating colonic inflammation are unclear. To identify these transcription factors, we mapped epigenomic changes in the colonic epithelium upon inflammation. Epigenetic marks at transcriptional regulatory elements responded dynamically to inflammation and indicated a shift in epithelial transcriptional factor networks. Active enhancer chromatin structure at regulatory regions bound by the transcription factor hepatocyte nuclear factor 4α (HNF4A) was reduced during colitis. In agreement, upon an inflammatory stimulus, HNF4A was downregulated and showed a reduced ability to bind chromatin. Genetic variants that confer a predisposition to IBD map to HNF4A binding sites in the human colon cell line CaCo2, suggesting impaired HNF4A binding could underlie genetic susceptibility to IBD. Despite reduced HNF4A binding during inflammation, a temporal knockout model revealed HNF4A still actively protects against inflammatory phenotypes and promotes immune regulatory gene expression in the inflamed colonic epithelium. These findings highlight the potential for HNF4A agonists as IBD therapeutics.
An Analysis of the Factors Affecting the Interaction between University and Industry (1995)

This paper discussed non-physical factors, such as the level of use of organizational channels and the level of R&D investment of the firm. It also explored physical factors such as the distance between the university and industry, transportation conditions between the two, and the availability (surplus capacity) of professors' or firms' research facilities that would affect the interaction such as the contacts in connection with research grants and consultations by professors to high-tech firms. This paper pointed out that the use of organization channel, the level of R&D investment, the availability research facilities of the university and high-tech firm, transportation conditions between the two, subject matter compatibility between professors' areas of expertise and firms' industrial activities, professors' (or staff) research capabilities and professors' (or staff) research times affect the interaction between the university and industry. It also found that the distance between the university and industry affects the interaction between the two in the opposite direction.
Seizure occurrence (2007)

Lack of sleep and higher self-reported stress and anxiety levels were associated with seizure occurrence. In a model that included self-prediction, less sleep, and self-prediction had significant effects, whereas stress and anxiety did not. The psychological and biologic mechanisms which link stress and anxiety to self-prediction of seizures requires further exploration. Ultimately, seizure prediction based on precipitants, premonitory features, and self-prediction may provide a foundation for preemptive treatment.
Treatment with a short course of LF 15‐0195 and continuous cyclosporin A attenuates acute xenograft rejection in a rat‐to‐mouse cardiac transplantation model (2003)

Searching for a novel immunosuppressive agent to effectively prevent acute vascular rejection (AVR) is essential for success in clinical xenotransplantation. We previously reported that Lewis rat hearts transplanted into BALB/c mice developed typical AVR in 6 days. The present study was undertaken to determine the efficacy of LF 15-0195, a new immunosuppressive analog of 15-deoxyspergualin in the prevention of AVR in a rat-to-mouse cardiac xenograft model. We transplanted 2-week old Lewis rat hearts into BALB/c mice. Four groups were included in this study: untreated recipients and cyclosporin A (CsA) treated recipients were controls; LF 15-0195 treated recipients or LF 15-0195 combined with CsA treated recipients were experimental groups. Mouse recipients received either LF 15-0195 2 mg/kg subcutaneously from day-1 to post-operative day 14, or CsA 15 mg/kg subcutaneously daily, from day 0 to endpoint rejection, or the two drugs in combination. We observed that high dose CsA did not inhibit AVR and the graft was rejected in 11.3 +/- 1.9 days. Graft histology and immunohistology showed typical AVR, characterized by interstitial hemorrhage, intravascular fibrin deposition, thrombosis, and massive deposition of anti-rat immunoglobulin G (IgG) and immunoglobulin M (IgM). Serum xenoreactive antibodies (xAbs) were markedly elevated in these animals as well. In contrast, we observed that treatment with LF 15-0195 alone significantly prolonged graft survival to 19.3 +/- 0.7 days. Notably, xAbs were significantly decreased and the rejection pattern of these grafts was cell-mediated rejection (CMR), instead of AVR. When CsA was combined with LF 15-0195, the graft mean survival time was further increased to 58.5 +/- 17.3 days. Antibody production and T-cell infiltration were significantly inhibited at the terminal stages of graft survival and pathology showed striking attenuation of both AVR and CMR. Sequential studies on days 6 and 14 demonstrated that LF 15-0195 either alone or combined with CsA completely inhibited antibody production. However, intragraft infiltration by Mac-1 positive cells including natural killer cells, macrophages and granulocytes in LF 15-0195 treated recipients was similar to that of untreated recipients. We conclude that LF 15-0195 effectively prevented AVR by markedly inhibiting the production of anti-donor IgG xAbs. Also, treatment with short course LF 15-0195 and continuous CsA significantly reduced T-cell infiltration. Studies to test this therapy in inhibiting AVR in a pig-to-non-human primate xenotransplantation model are underway.
Physical and Functional Association of Cortactin with Syk in Human Leukemic Cell Line K562 (1996)

Human leukemic cell line K562 is induced to differentiate into the megakaryocytic lineage by stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA). We demonstrate here that TPA stimulation increases tyrosine phosphorylation of an 80-kDa protein at an early stage of megakaryocytic differentiation and that this 80-kDa protein is identical with cortactin. Since tyrosine kinase Syk was activated by TPA stimulation, we examined the possibility that cortactin is a potential substrate of Syk in K562 cells. TPA-induced tyrosine phosphorylation of cortactin was decreased profoundly by overexpression of dominant-negative Syk. Furthermore, cortactin was associated with Syk even before TPA stimulation. Since cortactin was previously referred as an 80/85-kilodalton pp60src substrate, we examined the association between Src and cortactin, whereas its association could not be detected. These data suggest that Syk phosphorylates cortactin in K562 cells upon TPA treatment.
A wireless biosensing chip for DNA detection (2005)

A wireless sensing chip for biological assay is fully operational in a sample solution. The IC monolithically integrates a biological sensor, an RF communication circuit, and a coupling coil on a 2.5/spl times/2.5 mm/sup 2/ chip in 0.35 /spl mu/m CMOS technology. Detection of single nucleotide polymorphism (SNP) in DNA is successfully carried out by the chip.
RNA Interference in the Age of CRISPR: Will CRISPR Interfere with RNAi? (2016)

The recent emergence of multiple technologies for modifying gene structure has revolutionized mammalian biomedical research and enhanced the promises of gene therapy. Over the past decade, RNA interference (RNAi) based technologies widely dominated various research applications involving experimental modulation of gene expression at the post-transcriptional level. Recently, a new gene editing technology, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and the CRISPR-associated protein 9 (Cas9) (CRISPR/Cas9) system, has received unprecedented acceptance in the scientific community for a variety of genetic applications. Unlike RNAi, the CRISPR/Cas9 system is bestowed with the ability to introduce heritable precision insertions and deletions in the eukaryotic genome. The combination of popularity and superior capabilities of CRISPR/Cas9 system raises the possibility that this technology may occupy the roles currently served by RNAi and may even make RNAi obsolete. We performed a comparative analysis of the technical aspects and applications of the CRISPR/Cas9 system and RNAi in mammalian systems, with the purpose of charting out a predictive picture on whether the CRISPR/Cas9 system will eclipse the existence and future of RNAi. The conclusion drawn from this analysis is that RNAi will still occupy specific domains of biomedical research and clinical applications, under the current state of development of these technologies. However, further improvements in CRISPR/Cas9 based technology may ultimately enable it to dominate RNAi in the long term.
DNA Fountain enables a robust and efficient storage architecture (2017)

DNA is an attractive medium to store digital information. Here we report a storage strategy, called DNA Fountain, that is highly robust and approaches the information capacity per nucleotide. Using our approach, we stored a full computer operating system, movie, and other files with a total of 2.14 × 10<sup>6</sup> bytes in DNA oligonucleotides and perfectly retrieved the information from a sequencing coverage equivalent to a single tile of Illumina sequencing. We also tested a process that can allow 2.18 × 10<sup>15</sup> retrievals using the original DNA sample and were able to perfectly decode the data. Finally, we explored the limit of our architecture in terms of bytes per molecule and obtained a perfect retrieval from a density of 215 petabytes per gram of DNA, orders of magnitude higher than previous reports.