gebhart/patrepeval huggingface dataset:
The Success of Natural Products in Drug Discovery (2013)

Drug discovery leading to robust and viable lead candidates’ remains a challenging scientific task, which is the transition from a screening hit to a drug candidate, requires expertise and experience. Natural products and their derivatives have been recognized for many years as a source of therapeutic agents and of structural diversity. However, in addition to their chemical structure diversity and their biodiversity, the development of new technologies has revolutionized the screening of natural products in discovering new drugs. Applying these technologies compensates for the inherent limitations of natural products and offers a unique opportunity to re-establish natural products as a major source for drug discovery. The present article attempts to describe the utilization of compounds derived from natural resources as drug candidates, with a focus on the success of these resources in the process of finding and discovering new and effective drug compounds, an approach commonly referred to as “natural product drug discovery”.
The Effect of Surface Active Agents on the Relative Permeability of Brine and Gas in Porous Media (1995)

ABSTRACT Surface active agents are included in most aqueous treating fluids to improve the compatibility of aqueous fluids with the hydrocarbon containing reservoir. A review of the literature indicates very little core flow data to describe the effects to be expected. Traditionally, it is believed that the reduced surface tension will reduce capillary pressure and enhance the recovery of water after the treatment. The reduced water saturation is then believed to result in higher effective gas saturation and higher relative permeability to gas after the treatment.
High-resolution terahertz reflective imaging and image restoration (2010)

We present a high-resolution terahertz (THz) reflective imaging system, operating at 2.52 THz, that employs a continuous-wave THz gas laser and a pyroelectric detector. The spatial resolution was evaluated from the system's modulation transfer function and tested by scanning a series of resolution targets. To further improve the image quality, Lucy-Richardson method was adopted to restore the scanning result. With the scanning spot profile measured using knife edge method, a satisfying restoration result can be obtained. Finally, the system's performance was observed by imaging some different test objects.
The AMeX method: A multipurpose tissue‐processing and paraffin‐embedding method. III. Extraction and purification of RNA and application to slot‐blot hybridization analysis (1991)

RNA was extracted from tissues processed by a new fixation and paraffin-embedding method (the AMeX method) and examined by Northern blot analysis and slot-blot analysis. The RNA extraction method for AMeX-processed tissue sections after the deparaffinization step was the same as that for fresh materials. The total amount of cellular RNA extracted from AMeX-processed mouse liver tissue was slightly less than that extracted from fresh tissue. In tissues of malignant lymphoma, the total amount of cellular RNA extracted from 25 sections each 20 microns thick was about 1.6-1.8 micrograms/mm2, regardless of the histological subtype and period of storage. The extracted RNA was moderately degraded, and usually could not be used for Northern blot hybridization analysis. The intensity of ethidium bromide staining and the hybridization signals of RNA extracted from AMeX-processed tissues were usually reduced in comparison with RNA from fresh material, but specific signals could be detected by slot-blot hybridization analysis. We have demonstrated previously that the AMeX method preserves high-molecular-weight DNA and various antigens. Since the present study showed that information on mRNA can be obtained from AMeX-processed tissue, the versatility and usefulness of this method were further proven.
New high-nuclearity Ni–Pt carbonyl clusters: synthesis and X-ray structure of the ordered [Ni24Pt14(CO)44]4– and the substitutionally Ni/Pt disordered [Ni10(Ni6–xPtx)Pt8(CO)30]4– (x = 1.92) tetraanions (2001)

The reaction of [NnBu4]2[Ni6(CO)12] in THF solution with 1.5-2 equivalents of K2PtCl4 leads to formation of the [Ni24Pt14(CO)44]4- and [Ni10(Ni6-xPtx)Pt8(CO)30]4- (x approximately 2) tetraanions, the latter presents a localised substitutional Ni/Pt disorder and an unprecedented close-packed metal structure.
Regulation of a major cloned voltage&#x2010;gated K<sup>+</sup> channel from human T lymphocytes (1992)

When expressed into Xenopus oocytes, HLK3 K+ channel (Kv1-3) induced a slowly inactivating voltage-dependent K+ current. We have studied the modulation of this K+ current by co-expressing a cloned 5-HT2 receptor together with HLK3 K+ channel protein. Application of 5-HT caused a long-lasting inhibition of the voltage-gated K+ current. This inhibitory modulation was mimicked by intracellular injection of inositol triphosphate or Ca2+, as well as by incubation with phorbol esters or diacylglycerol analogs. Oocytes pretreatment with staurosporine and EGTA fully prevented 5-HT inhibitory action. Elevation of cAMP and cGMP levels into oocytes did not produce any detectable effect on the current recorded in the absence or the presence of 5-HT. These data suggest that the second messengers generated by phospholipase C activation may be important modulators of HLK3 K+ channels in the immune and the central nervous systems.
Microbial aerosol generation during laboratory accidents and subsequent risk assessment (2006)

A methodology has been described and supporting data provided to allow microbiological safety officers to carry out quantitative risk assessment of laboratory accidents.
Transforming growth factor β<sub>1</sub> expression in the endometrium of the mare during placentation (1995)

In situ hybridization, Northern blotting, and immunohistochemical techniques were used to study the expression of transforming growth factor beta 1 (TGF beta 1) in the endometrium of the mare during the first 150 days of pregnancy (term = 330-340 days). In situ hybridization using an oligonucleotide (45mer) probe, based on a homologous region within all known mammalian TGF beta 1 DNA sequences, demonstrated TGF beta 1 mRNA accumulation in the glandular and lumenal epithelial cells of the endometrium from day 33 onwards which corresponds to the time of implantation (day 33-45). Expression in the endometrium remained at a high level to the end of the sampling period (day 150). There was also marked expression of TGF beta 1 in the mononuclear cells accumulated around the periphery of the specialized trophoblast cells of the endometrial cup within the endometrium and in the mononuclear cells accumulated in the endometrial stroma of mares carrying failing donkey-in-horse pregnancies created by embryo transfer. The sense (control) oligonucleotide probe exhibited no hybridization to any tissue at any stage. Northern blot analysis demonstrated that the oligonucleotide probe and a porcine TGF beta 1 cDNA clone hybridized to a single 2.5 kb transcript in horse endometrial and lymphocyte RNA, thus validating the oligonucleotide probe for detection of horse TGF beta 1 mRNA. Furthermore, both probes demonstrated an increased signal in the pregnant endometrium from day 33 onwards, thereby confirming the in situ hybridization results. Immunostaining with a specific anti-bovine TGF beta 1 serum also showed increasing TGF beta 1 accumulation in endometrial epithelia during pregnancy, and localization of the protein in endometrial stroma and in the trophoblast layer of the placenta after day 60 of pregnancy. These results show that TGF beta 1 expression increases in the maternal endometrium of the mare at the time of implantation and that it may play a role in regulating endometrial and/or trophoblast growth and differentiation during placentation in this species. It may also influence fetal development (via placental transfer) at a later stage of gestation.
TCRep 3D: An Automated In Silico Approach to Study the Structural Properties of TCR Repertoires (2011)

TCRep 3D is an automated systematic approach for TCR-peptide-MHC class I structure prediction, based on homology and ab initio modeling. It has been considerably generalized from former studies to be applicable to large repertoires of TCR. First, the location of the complementary determining regions of the target sequences are automatically identified by a sequence alignment strategy against a database of TCR Vα and Vβ chains. A structure-based alignment ensures automated identification of CDR3 loops. The CDR are then modeled in the environment of the complex, in an ab initio approach based on a simulated annealing protocol. During this step, dihedral restraints are applied to drive the CDR1 and CDR2 loops towards their canonical conformations, described by Al-Lazikani et. al. We developed a new automated algorithm that determines additional restraints to iteratively converge towards TCR conformations making frequent hydrogen bonds with the pMHC. We demonstrated that our approach outperforms popular scoring methods (Anolea, Dope and Modeller) in predicting relevant CDR conformations. Finally, this modeling approach has been successfully applied to experimentally determined sequences of TCR that recognize the NY-ESO-1 cancer testis antigen. This analysis revealed a mechanism of selection of TCR through the presence of a single conserved amino acid in all CDR3β sequences. The important structural modifications predicted in silico and the associated dramatic loss of experimental binding affinity upon mutation of this amino acid show the good correspondence between the predicted structures and their biological activities. To our knowledge, this is the first systematic approach that was developed for large TCR repertoire structural modeling.
Cardiovascular risk factor control in Australia: current status and implications for the future. (2005)

The future for cardiovascular risk factor control in Australia needs to focus on optimising the use of therapeutic agents for risk factor reduction and promoting prevention programs. Major effort needs to be focussed on structural changes in general practice enabling prevention strategies directed toward lifestyle change to be recognised as a worthwhile investment. (non-author abstract)
The Thermosludge Water Treating and Steam Generation Process (1967)

Abstract The Thermosludge process internally softens and makes high-pressure steam directly from hard and saline oilfield or other water. Pilot plant and early full-scale plant work established several physical and chemical principles found necessary or desirable for good operation, and for control and practical elimination of scale on the process heating surfaces. These principles are use of a secondary liquid heat transfer medium, provision of time and space for water chemical reactions ahead of the boiling zone, and presence of sludged reaction products throughout the boiling zone. Other pertinent factors are discussed such as dissolved and suspended solids limits, foaming, corrosion, and heat transfer. Introduction In 1964 considerable use of steam in California oil fields was beginning to cause shortages of good steam generator feedwater in some areas. It seemed evident that in some situations oilfield brine or other low-quality water would have to be used to generate high-pressure steam directly. The Thermosludge process was developed to meet this need, and early results of its field use have been reported previously. This article discusses both pilot plant and full-scale plant design and operation particularly relative to the high-temperature reactions and scaling characteristics of some of the chemicals present in the waters. Present understanding of the process should allow broader use in its original field, and in other processing areas dealing with difficult waters. Pilot Plant Design and Operation After considerable study of chemical and engineering factors involved, a pilot plant program was set up. Three main theories or principles believed to lead to successful operation were followed in the pilot plant design and the same principles were carried into the full-scale plant design. First, heat should be applied via a secondary fluid heat transfer medium rather than directly in a combustion space. Relative to direct-fired beating, the secondary fluid heating guarantees that maximum tube wall temperature will be well within the allowable metal temperature limit regardless of local scaling or salting up. Many situations call for soluble salt in the steam generator in concentrations of as much as 15 percent by weight perhaps half of the limiting solubility. Even if conventional tube scaling were somehow entirely prevented, such situations would require the inherent heat flux control of a secondary heat medium to prevent gross fouling and plugging by salt deposits. Second, means should be provided in terms of high-temperature time and volume to preheat and chemically react the feedwater before it enters the boiling zone. The practicality of this is based on the expectation that thermally induced mineral sludging reactions will proceed much faster and more completely in the 350 to 600F environment than, for example, in the conventional lime-soda process. Thus, the feedwater should be entirely softened by the time it arrives at the boiling zone.
Biosynthesis of the cyanobacterial reserve polymer multi‐L‐arginyl‐poly‐L‐aspartic acid (cyanophycin) (2000)

Biosynthesis of the cyanobacterial nitrogen reserve cyanophycin (multi-L-arginyl-poly-L-aspartic acid) is catalysed by cyanophycin synthetase, an enzyme that consists of a single kind of polypeptide. Efficient synthesis of the polymer requires ATP, the constituent amino acids aspartic acid and arginine, and a primer like cyanophycin. Using synthetic peptide primers, the course of the biosynthetic reaction was studied. The following results were obtained: (a) sequence analysis suggests that cyanophycin synthetase has two ATP-binding sites and hence probably two active sites; (b) the enzyme catalyses the formation of cyanophycin-like polymers of 25-30 kDa apparent molecular mass in vitro; (c) primers are elongated at their C-terminus; (d) the constituent amino acids are incorporated stepwise, in the order aspartic acid followed by arginine, into the growing polymer. A mechanism for the cyanophycin synthetase reaction is proposed; (e) the specificity of the enzyme for its amino-acid substrates was also studied. Glutamic acid cannot replace aspartic acid as the acidic amino acid, whereas lysine can replace arginine but is incorporated into cyanophycin at a much lower rate.
The Assessing Patients’ Preferred Treatments (APPT-1) study (2003)

Limited information is currently available on patient preferences regarding administration frequency, tablet load and the trade-off between side effects and convenience in choosing antiretroviral regimens. A standardized questionnaire of persons with HIV infection across 5 large European countries was used to assess patient preference. 504 people with HIV participated. Participants showed a preference for once-daily therapy administration. However, several factors affected this preference.
Efficacy, durability, and response predictors of low-dose interleukin-2 therapy for chronic graft-versus-host disease (2016)

Chronic graft-versus-host disease (cGVHD) is associated with inadequate reconstitution of tolerogenic CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs). Previous phase 1 studies identified a low daily dose of interleukin-2 (IL-2) that was well tolerated, did not exacerbate alloimmunity, augmented Treg in vivo, and was associated with improvement of active cGVHD. In the current phase 2 study, 35 adults with steroid-refractory cGVHD received daily IL-2 (1 × 10(6) IU/m(2)) for 12 weeks. Median time from transplantation and cGVHD onset was 616 days (range, 270-2145 days) and 317 days (range, 28-1880 days), respectively. Two patients withdrew and 5 required IL-2 dose reductions due to side effects. Twenty of 33 evaluable patients (61%) had clinical responses at multiple cGVHD sites (liver, skin, gastrointestinal tract, lung, joint/muscle/fascia). Three patients (9%) had progressive cGVHD. Compared with pretreatment levels, Treg and natural killer cell counts rose >fivefold (P < .001) and >fourfold (P < .001), respectively, without significant change in conventional CD4 T cells (Tcons) or CD8 T cells. The Treg:Tcon ratio rose >fivefold (P < .001). Clinical responders initiated IL-2 earlier (508 vs 917 days after transplantation, P = .005; 249 vs 461 days after cGVHD onset; P = .03). Treg:Tcon ratios ≥0.07 at baseline and ≥0.2 at week 1 also predicted clinical response (P = .003; P = .0003, respectively). After a 4-week treatment hiatus, clinical responders were eligible to continue IL-2 therapy indefinitely. During 2 years of extended IL-2 therapy, clinical and Treg immune responses persisted, while Tcon count and Treg:Tcon ratio gradually normalized. Low-dose IL-2 provides durable clinical improvement in active cGVHD and extended therapy is well-tolerated.
Extracellular polymeric substances are transient media for microbial extracellular electron transfer (2017)

Microorganisms exploit extracellular electron transfer (EET) in growth and information exchange with external environments or with other cells. Every microbial cell is surrounded by extracellular polymeric substances (EPS). Understanding the roles of three-dimensional (3D) EPS in EET is essential in microbiology and microbial exploitation for mineral bio-respiration, pollutant conversion, and bioenergy production. We have addressed these challenges by comparing pure and EPS-depleted samples of three representative electrochemically active strains viz Gram-negative <i>Shewanella oneidensis</i> MR-1, Gram-positive <i>Bacillus</i> sp. WS-XY1, and yeast <i>Pichia stipites</i> using technology from electrochemistry, spectroscopy, atomic force microscopy, and microbiology. Voltammetry discloses redox signals from cytochromes and flavins in intact MR-1 cells, whereas stronger signals from cytochromes and additional signals from both flavins and cytochromes are found after EPS depletion. Flow cytometry and fluorescence microscopy substantiated by <i>N</i>-acetylglucosamine and electron transport system activity data showed less than 1.5% cell damage after EPS extraction. The electrochemical differences between normal and EPS-depleted cells therefore originate from electrochemical species in cell walls and EPS. The 35 ± 15-nm MR-1 EPS layer is also electrochemically active itself, with cytochrome electron transfer rate constants of 0.026 and 0.056 s<sup>-1</sup> for intact MR-1 and EPS-depleted cells, respectively. This surprisingly small rate difference suggests that molecular redox species at the core of EPS assist EET. The combination of all the data with electron transfer analysis suggests that electron "hopping" is the most likely molecular mechanism for electrochemical electron transfer through EPS.
Who competes with whom? A demand‐based perspective for identifying and representing asymmetric competition (2005)

Abstract A host of strategic management and marketing issues, including competitive analysis and strategic decision making, hinges on accurately identifying and representing competitive market structures. It is readily acknowledged that competitive market structures are typically asymmetric; namely, one firm may actively compete with another in a given market but not vice versa. However, empirical efforts to assess these competitive asymmetries have been lacking in the strategy literature. We propose a new spatial methodology to identify and represent asymmetric competitive market structures. Specifically, we devise a new stochastic multidimensional scaling procedure that is calibrated from actual consumer consideration/choice sets to estimate and uncover competitive asymmetries. The proposed methodology can be effectively employed in the analysis of appropriate data from either demand‐ or supply‐side approaches to assess competitive market structure. We illustrate our proposed methodology with survey data collected from two different commercial applications: one from the U.S. luxury automobile market and the other from the U.S. portable telephone market. We contrast the findings of the proposed methodology against traditional symmetric approaches for identifying and representing competitive market structures, and discuss the respective strategic insights. Copyright © 2005 John Wiley & Sons, Ltd.
Nano-indentation studies of ultrahigh strength carbon nitride thin films (1993)

Carbon nitride (CNx) thin films were prepared by dc magnetron sputtering of a graphite target in a nitrogen ambient onto Si(100) substrates held at ambient temperatures. The films are amorphous with a small volume fraction of nanocrystallites. All CNx coatings grown to a thickness of 1.5 μm are adherent and smooth. Nanoindentation studies showed clear dependence of hardness and effective modulus on deposition process parameters (nitrogen pressure, target power, and substrate bias). Most striking is the observation that CNx films can be synthesized with yield strength exceeding 5 GPa.
Prenatal allergic sensitization to helminth antigens in offspring of parasite-infected mothers. (1983)

Total and filaria-specific immunoglobulin E (IgE) levels were studied in cord blood from infants born in Madras, India, where filariasis and intestinal helminth infections are highly endemic. Increased total IgE levels were observed in 82% of 57 cord sera tested (geometric mean 12.6 ng/ml; range 1-1,900 ng/ml). 33 of these sera also contained IgE antibodies specific for filarial antigens as determined by solid-phase radioimmunoassay. Comparison of ratios of filaria-specific IgE to total IgE in paired maternal and cord sera suggested that cord blood IgE was derived from the fetus in most cases and not from transplacental antibody transfer. Our results suggest that prenatal allergic sensitization to helminth parasites occurs in the tropics. Such sensitization may contribute to the heterogeneity in host immune response and disease expression noted in filariasis and other helminth infections.
Differentiation of thymocytes in fetal organ culture: analysis of phenotypic changes accompanying the appearance of cytolytic and interleukin 2-producing cells. (1984)

At the 14th day of gestation, embryonic thymocytes+ are large, functionally incompetent cells with H-2K+ Thy-1+ B14- Ly-2- L3T4- phenotype, some of which express TL antigen. Differentiation of these cells in organ culture is characterized by: 1) appearance of cells expressing Ly-2 and L3T4 molecules, first among the population of large cells, after 2 days of culture; 2) appearance of small H-2K- Thy-1+TL+B14+Ly-2+L3T4+ and H-2K-Thy-1+TL+B14-Ly-2+ L3T4+ cells between days 2 and 4; 3) accumulation of small H-2K- Thy-1+ TL+ B14- Ly-2+ L3T4+ (but not H-2K- Thy-1+ TL+ B14+ Ly-2+ L3T4+) cells until day 5 of culture, and their subsequent gradual disappearance which is paralleled by an increase of the proportion of medium-sized H-2K+ Thy-1+ TL- B14- cells with various Ly-2 L3T4 phenotypes; 4) appearance and subsequent accumulation of cytolytic and IL 2-producing cells between days 4 and 6. Comparison of these results with the data from similar in vivo studies shows that differentiation of organ-cultured thymocytes rather closely follows the in vivo development only during the first week of culture and shows significant deviations thereafter. Precursors of cytolytic cells and cytolytic effector cells as well as IL 2-producing cells are found among both Ly-2+ and Ly-2- populations of thymocytes, indicating that there is no clear association between Ly-2 phenotype and the ability to kill or to secrete IL 2.