gebhart/patrepeval huggingface dataset:
Aromatic Small Molecules Remodel Toxic Soluble Oligomers of Amyloid β through Three Independent Pathways (2010)

In protein conformational disorders ranging from Alzheimer to Parkinson disease, proteins of unrelated sequence misfold into a similar array of aggregated conformers ranging from small oligomers to large amyloid fibrils. Substantial evidence suggests that small, prefibrillar oligomers are the most toxic species, yet to what extent they can be selectively targeted and remodeled into non-toxic conformers using small molecules is poorly understood. We have evaluated the conformational specificity and remodeling pathways of a diverse panel of aromatic small molecules against mature soluble oligomers of the Aβ42 peptide associated with Alzheimer disease. We find that small molecule antagonists can be grouped into three classes, which we herein define as Class I, II, and III molecules, based on the distinct pathways they utilize to remodel soluble oligomers into multiple conformers with reduced toxicity. Class I molecules remodel soluble oligomers into large, off-pathway aggregates that are non-toxic. Moreover, Class IA molecules also remodel amyloid fibrils into the same off-pathway structures, whereas Class IB molecules fail to remodel fibrils but accelerate aggregation of freshly disaggregated Aβ. In contrast, a Class II molecule converts soluble Aβ oligomers into fibrils, but is inactive against disaggregated and fibrillar Aβ. Class III molecules disassemble soluble oligomers (as well as fibrils) into low molecular weight species that are non-toxic. Strikingly, Aβ non-toxic oligomers (which are morphologically indistinguishable from toxic soluble oligomers) are significantly more resistant to being remodeled than Aβ soluble oligomers or amyloid fibrils. Our findings reveal that relatively subtle differences in small molecule structure encipher surprisingly large differences in the pathways they employ to remodel Aβ soluble oligomers and related aggregated conformers.
Expression cloning of an equine T‐lymphocyte glycoprotein CD2 cDNA (1994)

An equine CD2 cDNA has been isolated by monoclonal antibody screening of a T-lymphocyte cDNA library. The cDNA contained an open reading frame of 1041 bp encoding a translated product of 347 amino acids. Northern blotting analysis revealed a single mRNA species expressed in spleen, thymus and activated peripheral lymphocytes. The predicted amino acid sequence has 50-65% identity with the human, rat and mouse CD2 sequences with greatest similarity shared with the human homologue. Evolutionarily conserved structural and functional domains in CD2 were identified by comparing the sequences of the equine, human, mouse and rat CD2 homologues in the context of the recently derived crystal structure of rat soluble CD2 [Jones, E. Y., Davis, S. J., Williams, A. F., Harlos, K. & Stuart, D. I. (1992) Nature 360, 232-239]. The key conserved features of the extracellular region included core residues necessary to preserve the structural integrity of the molecule, residues in the linker region likely to maintain the unique domain organization of CD2, an array of highly charged residues in the putative ligand-binding face of the molecule and glycosylation-signal distributions that render the putative ligand-binding GFCC'C" face of domain 1 relatively unhindered by glycosylation.
Review article Testosterone therapy in the ageing male: what about the prostate? (2004)

The concerns about testosterone therapy in ageing men with late-onset hypogonadism mainly address the risk of prostatic disease, i.e. either benign prostatic hyperplasia (BPH) or prostate cancer (PCa). Both conditions are highly dependent on androgen action and recent clinical data on the cancer-preventive effect of the 5alpha-reductase inhibitor finasteride have supported the possible role of androgens in PCa. However, the clinical data especially on the long-term effects of exogenous androgen substitution in regard to prostate safety are nonconclusive in many respects. As sufficient clinical studies on these risks will not be available in the near future, the approach of testosterone therapy towards prostate complications should be kept on a safe but practical basis. This review includes some recommendations in regard to testosterone therapy and prostate monitoring in patients with BPH and bladder outlet obstruction, with previous history of curative treatment for PCa or with prostatic intraepithelial neoplasia.
Mechanical designs of active upper-limb exoskeleton robots: State-of-the-art and design difficulties (2009)

Active upper-limb exoskeleton robots have been developing from 1960s. In recent years, the mechanical designs and control algorithms of active upper-limb exoskeleton robots were developed significantly. This paper reviews the state-of-the-art of active upper-limb exoskeleton robots that are applied in the areas of rehabilitation and assistive robotics. In addition, the main requirements of the active upper-limb exoskeleton robot are identified and the mechanical designs of existing active upper-limb exoskeleton robot are classified. The design difficulties of an active upper-limb exoskeleton robot are discussed.
Transient receptor potential vanilloid 1, calcitonin gene-related peptide, and substance P mediate nociception in acute pancreatitis (2006)

The mechanism of pancreatitis-induced pain is unknown. In other tissues, inflammation activates transient receptor potential vanilloid 1 (TRPV1) on sensory nerves to liberate CGRP and substance P (SP) in peripheral tissues and the dorsal horn to cause neurogenic inflammation and pain, respectively. We evaluated the contribution of TRPV1, CGRP, and SP to pancreatic pain in rats. TRPV1, CGRP, and SP were coexpressed in nerve fibers of the pancreas. Injection of the TRPV1 agonist capsaicin into the pancreatic duct induced endocytosis of the neurokinin 1 receptor in spinal neurons in the dorsal horn (T10), indicative of SP release upon stimulation of pancreatic sensory nerves. Induction of necrotizing pancreatitis by treatment with L-arginine caused a 12-fold increase in the number of spinal neurons expressing the proto-oncogene c-fos in laminae I and II of L1, suggesting activation of nociceptive pathways. L-arginine also caused a threefold increase in spontaneous abdominal contractions detected by electromyography, suggestive of referred pain. Systemic administration of the TRPV1 antagonist capsazepine inhibited c-fos expression by 2.5-fold and abdominal contractions by 4-fold. Intrathecal, but not systemic, administration of antagonists of CGRP (CGRP(8-37)) and SP (SR140333) receptors attenuated c-fos expression in spinal neurons by twofold. Thus necrotizing pancreatitis activates TRPV1 on pancreatic sensory nerves to release SP and CGRP in the dorsal horn, resulting in nociception. Antagonism of TRPV1, SP, and CGRP receptors may suppress pancreatitis pain.
Retrograde amnesia in honeybees ( Apis mellifera carnica ). (1976)

After a single reward on a spectral color, freely flying honeybees show retrograde amnesia when an electroconvulsive shock, CO2 narcosis, N2 narcosis, or cooling (to 1 degrees C) is applied after learning. Retrograde amnesia is measurable with these four treatments up to 7 min after the reward. For none of the treatments was a consistent relationship found between the reaction tested and the time of testing after the treatment. Prolonged application of the four treatments leads to a significant increase in the rate of retrograde amnesia only after CO2 narcosis. Memory in the honeybee is susceptible to impairment until 15 min after the reward.
Efficient systemic therapy of rat glioblastoma by nanoparticle-bound doxorubicin is due to antiangiogenic effects (2009)

The objective of this study was to investigate the therapeutic effects of doxorubicin bound to polysorbate-coated nanoparticles that had previously been shown to significantly enhance survival in the orthotopic rat 101/8 glioblastoma model. Tumor-bearing animals were subjected to chemotherapy using doxorubicin in solution (Dox-sol) or doxorubicin bound to polysorbate 80-coated poly(butyl cyanoacrylate) nanoparticles (Dox-np) injected intravenously on Days 2, 5 and 8 post tumor implantation. The antitumor effect was assessed on Days 10, 14 and 18 post tumor implantation. Tumors showed signs of malignancy including invasion of brain tissue, brisk mitotic activity, microvascular proliferation, necrosis and increased proliferation resembling human glioblastoma. Dox-np produced a considerably more pronounced antitumor effect exhibited as a reduced tumor size, lower proliferation, and a decreased necrotic area compared to Dox-sol and to untreated control groups. A drastic effect of Dox-np on vascularization indicated an antiangiogenic mode of action.
Titelbild: Self‐Assembled DNA Nanoclews for the Efficient Delivery of CRISPR–Cas9 for Genome Editing (Angew. Chem. 41/2015) (2015)

Ein biologisch inspiriertes Transportsystem für CRISPR-Cas9, das auf Garn-ähnlichen DNA-Nanopartikeln, sogenannten DNA-Nanoknäueln basiert, wird von Z. Gu, C. L. Beisel et al. in der Zuschrift auf S. 12197 ff. beschrieben. DNA-Nanoknäuel (UFOs), die teilweise komplementär zur Single-guide-RNA (sgRNA) sind, wurden mit Cas9/sgRNA-Komplexen (Raketen) beladen und transportierten diese zum Genom-Editing in menschliche Zellen. Ein biologisch inspiriertes Transportsystem für CRISPR-Cas9, das auf Garn-ähnlichen DNA-Nanopartikeln, sogenannten DNA-Nanoknäueln basiert, wird von Z. Gu, C. L. Beisel et al. in der Zuschrift auf S. 12197 ff. beschrieben. DNA-Nanoknäuel (UFOs), die teilweise komplementär zur Single-guide-RNA (sgRNA) sind, wurden mit Cas9/sgRNA-Komplexen (Raketen) beladen und transportierten diese zum Genom-Editing in menschliche Zellen. Propylen-Epoxidierung Hauptgruppenchemie
Concrete Research Poetry: A Visual Representation of Metaphor (2017)

In this paper, the author employs concrete research poetry as a visual representation of a metaphor analysis. Using autoethnographic methods, she explores the experiences of eight single mothers of children and young adults with mental illness. She conducts a metaphor analysis of semi-structured interview data and generates concrete poetic structures from metaphors that emerged from the data. In the process, she transforms data into art.
De novo protein design using pairwise potentials and a genetic algorithm (1994)

One of the major goals of molecular biology is to understand how protein chains fold into a unique 3-dimensional structure. Given this knowledge, perhaps the most exciting prospect will be the possibility of designing new proteins to perform designated tasks, an application that could prove to be of great importance in medicine and biotechnology. It is possible that effective protein design may be achieved without the requirement for a full understanding of the protein folding process. In this paper a simple method is described for designing an amino acid sequence to fit a given 3-dimensional structure. The compatibility of a designed sequence with a given fold is assessed by means of a set of statistically determined potentials (including interresidue pairwise and solvation terms), which have been previously applied to the problem of protein fold recognition. In order to generate sequences that best fit the fold, a genetic algorithm is used, whereby the sequence is optimized by a stochastic search in the style of natural selection.
Lysogeny at Mid-Twentieth Century: P1, P2, and Other Experimental Systems (2004)

Most of us doing research have a preferred material, a set of well-tried techniques, a standing list of unsolved problems, ways of looking at or of doing things, which we share to a large extent with colleagues in the same laboratory and others in the same area of specialization, be they friends, former associates, or competitors. All this and more is encompassed by the concept of "experimental system" as introduced and used by Hans-Jörg Rheinberger (76, 77), a historian of science. His concept, rather flexible and rich in metaphors, may be easily adapted to the present narrative, which proceeds from a personal view rather than from a critical historical examination. A careful restriction of material, techniques, and nomenclature allows more constructive interactions between different laboratories and different generations of scientists in the same field. Of course, carried out to excess, this process will stifle developments in new areas and defer some discoveries. Max Delbrück, who in the early forties had forcefully advocated the study of bacteriophage as the royal road to the secrets of replication and recombination, was quite outspoken about the necessity for workers on that road to use a common material (the T phages in Escherichia coli B) and precisely standardized techniques (1). Of course, the T phages are generally virulent, take-no-prisoner parasites of bacteria and thus could not instruct us about the more shadowy interactions between "weaker" bacteriophages and their bacterial hosts: about lysogeny, where infection meets heredity.
Mosquitocidal Activity of Leaf and Bark Essential Oils of CeylonCinnamomum zeylanicum (2005)

Abstract Mosquito control properties of essential oils of leaf and bark of Ceylon Cinnamomum zeylanicum Blume (Lauraceae) and their eight compounds were investigated against Culex quinquefasciatus, Anopheles tessellatus and Aedes aegypti. Cinnamomum zeylanicum bark oil showed good knock-down and mortality against A. tessellatus (LD50 0.33 μg/mL) and C. quinquefasciatus (LD50 0.66 μg/mL) than leaf oil (LD50 1.03 and 2.1 μg/mL). Cinnamaldehyde was a major constituent of the bark oil and eugenol in the leaf oil. Cinnamaldehyde and eugenol both were more active against C. quinquefasciatus, A. tessellatus and A. aegypti than the bark and leaf oil. Mosquitocidal activity of cinnamyl acetate against three mosquito species was comptarable to that of the Cinnamomum bark oil, whereas eugenyl acetate was effective on A. tessellatus and C. quinquefasciatus. The other compounds showed less or no activity against mosquitoes tested.
Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: Is resection still the treatment of choice? (2007)

Compared with resection, RFA is less invasive and associated with lower complication rate and lower costs. RFA is also just as effective for ensuring local control of stage T1 HCC, and it is associated with similar survival rates (as recently demonstrated by 2 randomized trials). These data indicate that RFA can be considered the treatment of choice for patients with single HCC <or= 2.0 cm, even when surgical resection is possible. Other approaches can be used as salvage therapy for the few cases in which RFA is unsuccessful or unfeasible.
Salmonella typhimurium phoP virulence gene is a transcriptional regulator. (1989)

Salmonella typhimurium is a facultative intracellular pathogen capable of surviving within host phagocytic cells. Salmonella strains carrying phoP mutations are avirulent, unable to survive in macrophages, and extremely sensitive to peptides having antimicrobial activity such as the host-derived defensins. We present here the DNA sequence of the phoP gene and show that the deduced amino acid sequence of phoP has extensive homology with the Escherichia coli transcriptional regulators PhoB and OmpR, which control the expression of loci in response to different environmental stimuli. The psiD locus, which is regulated by phosphate availability, was found to be under the control of the phoP gene product. Sequences homologous to phoP were found in several Gram-negative species and in the yeast Saccharomyces cerevisiae.
Thermal and plasma wave depth profiling in silicon (1985)

We describe a depth-profiling concept using the critically damped plasma wave corresponding to the propagation of the free-carrier plasma density generated by a modulated laser in a semiconductor.
MercuryII-Mediated Formation of Thymine−HgII−Thymine Base Pairs in DNA Duplexes (2006)

The very specific binding of the HgII ion unexpectedly and significantly stabilizes naturally occurring thymine-thymine base mispairing in DNA duplexes. Following this finding, we prepared DNA duplexes containing metal-mediated base pairs at the desired sites, as well as novel double helical architectures consisting only of thymine-HgII-thymine pairs.
Mutations of the p53 gene in the stool of patients with resectable colorectal cancer (1996)

This method of stool DNA analysis for tumor-specific mutations is expected to have a wide application in clinical screening for colorectal cancer.
Effect of IGF-I in the Chondrogenesis of Bone Marrow Mesenchymal Stem Cells in the Presence or Absence of TGF-β Signaling (2006)

IGF-I modulated MSC chondrogenesis by stimulating proliferation, regulating cell apoptosis, and inducing expression of chondrocyte markers. IGF-I chondroinductive actions were equally potent to TGF-beta1, and the two growth factors had additive effects. Using RIIKO-MSCs, we showed that IGF-I chondrogenic actions are independent from the TGF-beta signaling. We found that the extracellular signal-related kinase 1/2 mitogen-activated protein kinase (Erk1/2 MAPK) pathway mediated the TGF-beta1 mitogenic response and in part the IGF-I proliferative action. Our data, by showing the role of IGF-I and TGF-beta1 in the critical steps of MSC chondrogenesis, provide critical information to optimize the therapeutic use of MSCs in cartilage disorders.
Development of micropatterning technology for cultured cells. (1991)

The manipulation of regional cell adhesiveness by surface design could provide micropatterned cell culturing. Based on the photoreactive chemistry of a phenylazide group, a novel surface micropatterning technology for cultured cells was successfully developed. The principle is as follows: 1) a photoreactive hydrophilic co-polymer with phenylazide was cast on a hydrophobic matrix surface, 2) a photoreactive hydrophobic co-polymer was cast on a hydrophilic matrix; 3) a photomask with a given pattern was tightly placed on the cast film; and 4) after UV irradiation and subsequent washing, bovine endothelial cells (ECs) were seeded and cultured. ECs adhered and grew only on nonhydrophilic regions, eventually resulting in micropatterning of ECs. The micropatterns of cultured ECs prepared by 1) and 2) were negative- and positive-type patterns to that of the photomask used, respectively.
Genetic engineering of doxorubicin production in Streptomyces peucetius : a review (1999)

The genetics and biochemistry of daunorubicin and doxorubicin production by Streptomyces peucetius is reviewed, with a focus on how such information can be used for the genetic engineering of strains having improved titers of these two antitumor antibiotics.
Lymphocyte depletion during treatment with intensive chemotherapy for cancer (1994)

Abstract Recently we have observed an increased incidence of opportunistic infections in patients treated with intensive chemotherapy for cancer. Because T-cell depletion is associated with similar clinical events in human immunodeficiency virus infection and after bone marrow transplantation, we have analyzed peripheral blood lymphocyte populations in a series of patients during treatment with intensive chemotherapy for cancer. Although neutrophil, monocyte, and platelet numbers consistently recovered to greater than 50% of pretreatment values after each sequential cycle of therapy, lymphocyte numbers did not recover within the same time period. B cells decreased rapidly from a mean value of 149 +/- 46/mm3 before chemotherapy to 4 +/- 1/mm3 during chemotherapy (P = .01). CD4+ T cells decreased from a mean of 588 +/- 76/mm3 before chemotherapy to 105 +/- 28/mm3 during chemotherapy (P = .0002) and CD8+ T cells decreased from a mean of 382 +/- 41/mm3 before chemotherapy to 150 +/- 46/mm3 during chemotherapy (P = .0009). Natural killer cell numbers did not show significant declines (171 +/- 30/mm3 before, 114 +/- 24/mm3 during, P = .19). Based on the history of opportunistic complications in patients with other disorders who display similar degrees of CD4+ T-cell lymphopenia and preliminary observations in this population, immune incompetence could surface as a dose-limiting toxicity for highly dose-intensive chemotherapy regimens.
Terra (2003)

We present a flexible architecture for trusted computing, called Terra, that allows applications with a wide range of security requirements to run simultaneously on commodity hardware. Applications on Terra enjoy the semantics of running on a separate, dedicated, tamper-resistant hardware platform, while retaining the ability to run side-by-side with normal applications on a general-purpose computing platform. Terra achieves this synthesis by use of a trusted virtual machine monitor (TVMM) that partitions a tamper-resistant hardware platform into multiple, isolated virtual machines (VM), providing the appearance of multiple boxes on a single, general-purpose platform. To each VM, the TVMM provides the semantics of either an "open box," i.e. a general-purpose hardware platform like today's PCs and workstations, or a "closed box," an opaque special-purpose platform that protects the privacy and integrity of its contents like today's game consoles and cellular phones. The software stack in each VM can be tailored from the hardware interface up to meet the security requirements of its application(s). The hardware and TVMM can act as a trusted party to allow closed-box VMs to cryptographically identify the software they run, i.e. what is in the box, to remote parties. We explore the strengths and limitations of this architecture by describing our prototype implementation and several applications that we developed for it.
Morphologic and biochemical hallmarks of apoptosis (2000)

Apoptosis is characterised by a series of typical morphological features, such as shrinkage of the cell, fragmentation into membrane-bound apoptotic bodies and rapid phagocytosis by neighbouring cells. This paper reviews the current knowledge on the molecular mechanisms of apoptosis as they relate to the morphologic hallmarks and their implications for the detection of apoptosis in cardiac tissue. Activation of cysteine proteases called caspases plays a major role in the execution of apoptosis. These proteases selectively cleave vital cellular substrates, which results in apoptotic morphology and internucleosomal fragmentation of DNA by selectively activated DNases. In response to several pro-apoptotic signals, mitochondria release caspase activating factors, that initiate an escalating caspase cascade and commit the cell to die. Members of the Bcl-2 oncoprotein family control mitochondrial events and are able to prevent, or induce, both apoptotic and non-apoptotic types of cell death. This suggests that different types of cell death share common mechanisms in the early phases, whereas activation of caspases determines the phenotype of cell death. Detection of apoptotic cells in tissue samples currently relies on the TUNEL assay. TUNEL-positive cardiomyocytes show morphological features of apoptosis and the typical ladder pattern in DNA electrophoresis. Thus, provided that the staining protocol is carefully standardised, this quantitative methodology provides reproducible results of the occurrence of cardiomyocyte apoptosis in cardiac samples. Recently, potentially more specific assays based on analysis of DNA fragmentation or demonstration of caspase activation have been developed. Applicability of these assays to demonstrate cardiomyocyte apoptosis should be tested.