gebhart/patrepeval huggingface dataset:
Zinc finger nucleases: custom-designed molecular scissors for genome engineering of plant and mammalian cells (2005)

Custom-designed zinc finger nucleases (ZFNs), proteins designed to cut at specific DNA sequences, are becoming powerful tools in gene targeting--the process of replacing a gene within a genome by homologous recombination (HR). ZFNs that combine the non-specific cleavage domain (N) of FokI endonuclease with zinc finger proteins (ZFPs) offer a general way to deliver a site-specific double-strand break (DSB) to the genome. The development of ZFN-mediated gene targeting provides molecular biologists with the ability to site-specifically and permanently modify plant and mammalian genomes including the human genome via homology-directed repair of a targeted genomic DSB. The creation of designer ZFNs that cleave DNA at a pre-determined site depends on the reliable creation of ZFPs that can specifically recognize the chosen target site within a genome. The (Cys2His2) ZFPs offer the best framework for developing custom ZFN molecules with new sequence-specificities. Here, we explore the different approaches for generating the desired custom ZFNs with high sequence-specificity and affinity. We also discuss the potential of ZFN-mediated gene targeting for 'directed mutagenesis' and targeted 'gene editing' of the plant and mammalian genome as well as the potential of ZFN-based strategies as a form of gene therapy for human therapeutics in the future.
A General and Adaptive Robust Loss Function (2019)

We present a generalization of the Cauchy/Lorentzian, Geman-McClure, Welsch/Leclerc, generalized Charbonnier, Charbonnier/pseudo-Huber/L1-L2, and L2 loss functions. By introducing robustness as a continuous parameter, our loss function allows algorithms built around robust loss minimization to be generalized, which improves performance on basic vision tasks such as registration and clustering. Interpreting our loss as the negative log of a univariate density yields a general probability distribution that includes normal and Cauchy distributions as special cases. This probabilistic interpretation enables the training of neural networks in which the robustness of the loss automatically adapts itself during training, which improves performance on learning-based tasks such as generative image synthesis and unsupervised monocular depth estimation, without requiring any manual parameter tuning.
The Janus face of cyclophosphamide (2013)

Cyclophosphamide, within well-defined therapeutic regimens, increases the antineoplastic effects of immunotherapy. We have recently identified multiple factors and mechanisms that underlie the paradoxical synergy between these two treatment modalities. In particular, we found that cyclophosphamide stimulates anticancer immune responses upon the perception by the immune system of inflammatory danger signals associated with the death of leukocytes, via p53 and type I interferon-related mechanisms.
Experimental intramammary inoculation with Mycoplasma bovis in vaccinated and unvaccinated cows: effect on milk production and milk quality. (1986)

The effect of vaccination on milk production was evaluated in vaccinated and control cows experimentally challenged in two of four quarters with live Mycoplasma bovis. During the first three weeks after experimental challenge, six of eight unchallenged quarters on vaccinated cows and seven of eight unchallenged quarters on control cows became infected. Most of these quarters secreted normal milk, with negative California Mastitis Test scores and maintained normal milk production throughout most of the study (although some quarters on control cows remained infected). All challenged quarters became infected, had strong California Mastitis Test reactions, and had a drastic (greater than 85%) loss in milk production. Thereafter, four of eight challenged quarters on control cows remained infected, had mostly positive California Mastitis Test scores, produced mostly normal-appearing milk, and recovered some productive capabilities. By the end of the study no M. bovis could be recovered from challenged quarters on vaccinated cows and the milk appeared mostly normal. The California Mastitis Test scores on these quarters, however, remained elevated and milk production remained very low.
Design of a solid-state file using flash EEPROM (1995)

This paper presents dynamic sector allocation, clustered sector allocation, and background garbage collection--mechanisms that are key algorithms in solid-state files (SSFs) using flash EEPROMs. Dynamic sector allocation resembles a log-structured file system, which sequentially writes all data modifications to the SSF. Clustered sector allocation is a technique for using the dynamic sector allocation mechanism in an SSF that incorporates a NAND flash EEPROM architecture. Dynamic sector allocation inevitably accumulates obsolete data on the SSF. This “garbage” must be erased in order to secure free space on the SSF. The garbage collection mechanism is a free-space-management method performed as a background process in the SSF. These three mechanisms are closely related and work collaboratively to enable flash EEPROMs to perform well in spite of the serious inherent limitations of the devices. We simulated the behavior of several SSFs and observed that 30% of the storage area of the SSFs must be used as a work area in order to ensure an acceptably low rate of memory-erase operations. We also demonstrated that the lifetime of the SSF is long enough for use in most personal computers. Finally, we have developed SSFs using the NAND type of flash EEPROMs that incorporate the above mechanisms.
Use of amphipathic polymers to deliver a membrane protein to lipid bilayers (2001)

Data are presented which suggest that a class of amphiphilic polymers known as 'amphipols' may serve as a vehicle for delivering complex integral membrane proteins into membranes. The integral membrane protein diacylglycerol kinase (DAGK) was maintained in soluble form by either of two different amphipols. Small aliquots of these solutions were added to pre-formed lipid vesicles and the appearance of DAGK catalytic activity was monitored as an indicator of the progress of productive protein insertion into the bilayers. For one of the two amphipols tested, DAGK was observed to productively transfer from its amphipol complex into vesicles with moderate efficiency. Results were not completely clear for the other amphipol.
A zebrafish retinoic acid receptor expressed in the regenerating caudal fin (1994)

Retinoic acid (RA) is an important signalling molecule in vertebrate pattern formation both in developing and regenerating tissues. The effects of RA are due largely to regulation of gene transcription, mediated by retinoic acid receptors (RAR-alpha, RAR-beta, RAR-gamma) and retinoid X receptors (RXR-alpha, RXR-beta, RXR-gamma). We have been using zebrafish as a model of regeneration to study the role of retinoic acid and its receptors in vertebrate pattern formation. In this report, we describe the molecular cloning and characterization of one of the zebrafish RARs that is the predominant receptor in the regenerating caudal fin and corresponds most closely to the RAR-gamma subtype isolated from mouse and human and to RAR-delta from newt. Zebrafish RAR-gamma (zfRAR-gamma) exhibits both structural and functional conservation with its mammalian counterparts. Studies utilizing both normal and regenerating caudal fins of the zebrafish have indicated that it is the RAR-gamma subtype, compared to RAR-alpha or RAR-beta, which is expressed at the highest levels in the tail fin. To localize the expression pattern of RAR-gamma during fin regeneration, we have carried out whole-mount in situ hybridization. ZfRAR-gamma transcripts, during fin regeneration, are localized in the blastemal tissue formed at the distal ends of the bony rays following amputation. Treatment of fish with RA during fin regeneration induces a number of striking morphological effects on the regenerate. When amputations are performed distal to the branch points or dichotomies, where a single ray bifurcates to extend two individual 'daughter' rays, RA treatment causes a dichotomy reduction where the two 'daughter' rays fuse to once again form a single ray. The single ray subsequently bifurcates in a comparatively normal manner. Our data suggest that exogenous RA can respecify pattern in the regenerating caudal fin and identifies the blastemae as possible RA target tissues.
How irritant is water? An overview (1999)

Water is a skin irritant which deserves attention because of its ubiquity. During the Vietnam war, soldiers suffered from painful swollen feet, so-called tropical immersion foot. In occupational dermatology, the importance of water as a skin irritant is especially appreciated. The irritancy of water has been demonstrated by occlusion experiments; occlusion with either closed chambers or water-soaked patches has been shown to produce clinical and histopathological inflammation. Functional damage, as revealed by increased transepidermal water loss, has also been shown. Repeated water exposure without occlusion caused an increase in blood flow on irritated skin; however, clinical evaluation did not show a difference in dryness or scaling. Several mechanisms such as osmolarity, pH, hardness and temperature might account for the irritancy of water. Extraction or dilution of natural moisturizing factors in the stratum corneum is another possible explanation. Occlusion per se also changes the physiology of skin and may trigger the activation of potentially active substances. However, much remains to be done to clarify the risk factors and mechanisms of water-induced irritation.
Optimal frequency of carotid sinus nerve stimulation in treatment of angina pectoris (1974)

Carotid sinus nerve stimulation (CSNS) was applied in seven angina pectoris patients for periods of 1–2 min, using a modified Angistat (Medtronic) stimulator at frequencies ranging from 20 to 200 Hz. Stimulation at frequencies between 80 and 120 Hz elicited the largest increase in R-R interval and blood pressure reduction. Due to technical limitations of the device, the Angistat stimulator appears to be unsuitable if stimulation frequencies in excess of 120 Hz are to be applied. We conclude that the optimal frequency of the Angistat CSNS stimulator in the treatment of angina pectoris is between 80 and 120 Hz.
Rapid retrovirus titration using competitive polymerase chain reaction. (1996)

A quantitative polymerase chain reaction (PCR) procedure has been developed for rapid retrovirus titration. This procedure, which is based on the simultaneous amplification of the sample with known amounts of a competitor DNA fragment (competitive PCR), was used for the quantification of viral RNA genomes in retrovirus-producing cell clone supernatants and of proviral DNA molecules formed at 24 h after infection of different reference cell lines. The results obtained from the analysis of several samples indicated that proviral DNA quantification is in complete agreement with the number of selectable colonies in a standard colony assay. Conversely, the number of viral RNA genomes in the producer cell clone supernatants is a poor predictor of the actual efficiency of infection. Repeated competitive PCR experiments for provirus copy number determination at different times after transduction indicated that the number of proviral DNA molecules remains stable over time, suggesting stable integration into the host genome. The developed procedure is rapid and simple, is applicable to retroviral constructs not containing a selectable gene and can be used to directly measure the efficiency of infection of any target cell type, thus overcoming the problem of the dependency of retroviral titer determination on the rate of expression of a selectable gene and on the efficiency of colony formation of a reference cell line.
A novel RT‐PCR for reliable and rapid HCV RNA screening of blood donations (2001)

The TaqMan HCV RT-PCR is an almost completely automated, highly sensitive, specific, and rapid method that is reliable for HCV RNA screening of blood donations. It allows a closed-tube HCV RNA detection without risk of contamination by PCR products.
Gastrin and Somatostatin Levels in Patients with Gastric Cancer (1989)

Gastrin and somatostatin-like immunoreactivity (SLI) levels were studied by means of radioimmunoassay in peripheral venous blood of healthy volunteers and patients suffering from gastric adenocarcinoma or duodenal and gastric ulcers. Gastrin and SLI levels were also evaluated in patients in blood drawn from gastric veins during surgery. The elevations of gastrin and SLI levels were found in patients with gastric cancer as compared with healthy people and patients suffering from ulcers. The impairment of the negative feedback between gastrin and somatostatin secretions in patients with gastric cancer was suggested.
Über Thiazole, XLVI. Folgeprodukte der Thiazolyl‐(2)‐cyanamide (1966)

Abstract Durch Addition nucleophiler Reaktionspartner, wie H 2 S, H 2 O, Anilin und Hydrazin, an die CN‐Gruppe der Thiazolyl‐(2)‐cyanamide ( 1 ) erhält man Thiazolyl‐(2)‐thioharnstoffe ( 2 ), Thiazolyl‐(2)‐harnstoffe ( 3 ), 3‐Phenyl‐1‐[thiazolyl‐(2)]‐ ( 4 ) und 3‐Amino‐1‐[thiazolyl‐(2)]‐guanidine ( 5 ). Letztere bilden mit Acetessigester über die Hydrazone ( 7 ) 1‐substituierte 3‐Methyl‐pyrazolone‐(5) ( 8 ).
Capacitance extraction of 3-D conductor systems in dielectric media with high-permittivity ratios (1999)

We describe a perturbation formulation for the problem of computing electrostatic capacitances of multiple conductors embedded in multiple dielectric materials. Unlike the commonly used equivalent-charge formulation (ECF), this new approach insures that the capacitances are computed accurately even when the permittivity ratios of the dielectric materials are very large. Computational results from a three-dimensional multipole-accelerated algorithm based on this approach are presented. The results show that the accuracy of this new approach is nearly independent of the permittivity ratios and superior to the ECF for realistic interconnect structures.
Vascular amine oxidases are needed for leukocyte extravasation into inflamed joints in vivo (2006)

These are the first data to demonstrate that the enzymatic activity of the atypical endothelial adhesion molecule AOC3, and possibly that of other closely related ecto-oxidases, is crucial for leukocyte exit from the vessels in inflamed joints in vivo.
Heparin binding to platelet factor-4. An NMR and site-directed mutagenesis study: arginine residues are crucial for binding (1995)

Native platelet factor-4 (PF4) is an asymmetrically associated, homo-tetrameric protein (70 residues/subunit) known for binding polysulphated glycosaminoglycans like heparin. PF4 N-terminal chimeric mutant M2 (PF4-M2), on the other hand, forms symmetric tetramers [Mayo, Roongta, Ilyina, Milius, Barker, Quinlan, La Rosa and Daly (1995) Biochemistry 34, 11399-11409] making NMR studies with this 32 kDa protein tractable. PF4-M2, moreover, binds heparin with a similar affinity to that of native PF4. NMR data presented here indicate that heparin (9000 Da cut-off) binding to PF4-M2, while not perturbing the overall structure of the protein, does perturb specific side-chain proton resonances which map to spatially related residues within a ring of positively charged side chains on the surface of tetrameric PF4-M2. Contrary to PF4-heparin binding models which centre around C-terminal alpha-helix lysines, this study indicates that a loop containing Arg-20, Arg-22, His-23 and Thr-25, as well as Lys-46 and Arg-49, are even more affected by heparin binding. Site-directed mutagenesis and heparin binding data support these NMR findings by indicating that arginines more than C-terminal lysines, are crucial to the heparin binding process.
Rapid procedure for detection and isolation of large and small plasmids (1981)

Procedures are described for the detection and isolation of plasmids of various sizes (2.6 to 350 megadaltons) that are harbored in species of Agrobacterium, Rhizobium, Escherichia, Salmonella, Erwinia, Pseudomonas, and Xanthomonas. The method utilized the molecular characteristics of covalently closed circular deoxyribonucleic acid (DNA) that is released from cells under conditions that denature chromosomal DNA by using alkaline sodium dodecyl sulfate (pH 12.6) at elevated temperatures. Proteins and cell debris were removed by extraction with phenol-chloroform. Under these conditions chromosomal DNA concentrations were reduced or eliminated. The clarified extract was used directly for electrophoretic analysis. These procedures also permitted the selective isolation of plasmid DNA that can be used directly in nick translation, restriction endonuclease analysis, transformation, and DNA cloning experiments.
Activation of a Plasma Membrane–Associated Neutral Sphingomyelinase and Concomitant Ceramide Accumulation During IgG-Dependent Phagocytosis in Human Polymorphonuclear Leukocytes (1998)

The sphingomyelin cycle, which plays an important role in regulation of cell growth, differentiation, and apoptosis, involves the formation of ceramide by the action of a membrane-associated, Mg2+-dependent, neutral sphingomyelinase and/or a lysosomal acid sphingomyelinase. In human polymorphonuclear leukocytes (PMNs), ceramide production correlates with and plays a role in the regulation of functional responses such as oxidant release and Fcγ receptor-mediated phagocytosis. To increase our understanding of the sphingomyelin cycle in human PMNs, the cellular location of neutral and acid sphingomyelinases was investigated in resting, formylmethionylleucylphenylalanine (FMLP)-activated, and FMLP-activated PMNs engaged in phagocytosis. In resting PMNs, a Mg2+-dependent, neutral sphingomyelinase was the predominant activity and was localized to the plasma membrane fractions along with the majority of ceramide. Upon FMLP-activation, there was a 1.9-fold increase in this neutral, Mg2+-dependent sphingomyelinase activity, which increased to 2.7-fold subsequent to phagocytosis of IgG opsonized targets. This increase in sphingomyelinase activity was restricted to the plasma membrane fractions, which were also the site of increased ceramide levels. Phospholipase D (PLD) activity, which is a target of ceramide action and is required for phagocytosis, was also found primarily in the plasma membrane fractions of FMLP-activated and phagocytosing PMNs. Our findings indicate that in human PMNs engaged in phagocytosis, the sphingomyelin cycle is restricted to the plasma membrane where intracellular targets of ceramide action, such as PLD, are localized.
Improved method for the Wacker oxidation of cyclic and internal olefins (1990)

Peer reviewed: Yes
The Magic of the Z-Buffer: A Survey (2001)

Interprofessional PAL can increase knowledge and confidence of healthcare students reciprocally learning and teaching in joint activities. Allowing such interactions facilitate students to build interprofessional relationships during their training, which can increase communication and collaboration to foster an appreciation for each other's roles in clinical practice.
Electrolytic charge inversion at the liquid–solid interface in a nanopore in a doped semiconductor membrane (2007)

The electrostatics of a nanopore in a doped semiconductor membrane immersed in an electrolyte is studied with a numerical model. Unlike dielectric membranes that always attract excess positive ion charges at the electrolyte/membrane interface whenever a negative surface charge is present, semiconductor membranes exhibit more versatility in controlling the double layer at the membrane surface. The presence of dopant charge in the semiconductor membrane, the shape of the nanopore and the negative surface charge resulting from the pore fabrication process have competing influences on the double layer formation. The inversion of the electrolyte surface charge from negative to positive is observed for n-Si membranes as a function of the membrane surface charge density, while no such inversion occurs for dielectric and p-Si membranes.
Complete Genome Sequence of Yersinia pestis Strains Antiqua and Nepal516: Evidence of Gene Reduction in an Emerging Pathogen (2006)

ABSTRACT Yersinia pestis , the causative agent of bubonic and pneumonic plagues, has undergone detailed study at the molecular level. To further investigate the genomic diversity among this group and to help characterize lineages of the plague organism that have no sequenced members, we present here the genomes of two isolates of the “classical” antiqua biovar, strains Antiqua and Nepal516. The genomes of Antiqua and Nepal516 are 4.7 Mb and 4.5 Mb and encode 4,138 and 3,956 open reading frames, respectively. Though both strains belong to one of the three classical biovars, they represent separate lineages defined by recent phylogenetic studies. We compare all five currently sequenced Y. pestis genomes and the corresponding features in Yersinia pseudotuberculosis . There are strain-specific rearrangements, insertions, deletions, single nucleotide polymorphisms, and a unique distribution of insertion sequences. We found 453 single nucleotide polymorphisms in protein-coding regions, which were used to assess the evolutionary relationships of these Y. pestis strains. Gene reduction analysis revealed that the gene deletion processes are under selective pressure, and many of the inactivations are probably related to the organism's interaction with its host environment. The results presented here clearly demonstrate the differences between the two biovar antiqua lineages and support the notion that grouping Y. pestis strains based strictly on the classical definition of biovars (predicated upon two biochemical assays) does not accurately reflect the phylogenetic relationships within this species. A comparison of four virulent Y. pestis strains with the human-avirulent strain 91001 provides further insight into the genetic basis of virulence to humans.
Pyrylenes: A New Class of Tunable, Redox-Switchable, Photoexcitable Pyrylium–Carbene Hybrids with Three Stable Redox-States (2018)

A new synthetic and modular access to a large family of redox-switchable molecules based upon the combination of pyrylium salts and carbenes is presented. The redox-properties of this new molecule class correlate very well with the π-accepting properties of the corresponding carbenes. While the pyrylium moiety acts as a chromophore, the carbene moiety can tune the redox-properties and stabilize the corresponding radicals. This leads to the isolation of the first monomeric pyranyl-radical in the solid-state. The three stable oxidation states could be cleanly accessed by chemical oxidation, characterized by NMR, EPR, UV-vis, and X-ray diffraction and supported by (TD)-DFT-calculations. The new hybrid class can be utilized as an electrochemically triggered switch and as a powerful photoexcited reductant. Importantly, the pyrylenes can be used as novel photocatalysts for the reductive activation of aryl halides and sulfonamides by consecutive visible light induced electron transfer processes.