gebhart/patrepeval huggingface dataset:
Sequence of an antifreeze protein precursor (1984)

The amino acid sequence of the precursor to the second-most-abundant serum antifreeze protein (B) in the winter flounder has been determined by a combination of protein and DNA sequencing. The precursor is an 82-residue preproprotein which differs in only three positions from the amino acid sequence of the precursor for the most-abundant serum antifreeze protein (A). The base changes responsible for these substitutions, as well as several silent changes, are all clustered within the DNA coding for the mature protein portion. Among the post-translational modifications that the precursor undergoes is the removal of the c-terminal glycine residue. Cloning of full-length antifreeze protein cDNA has enabled us to identify the transcription initiation site which occurs 49 nucleotides upstream from the initiation codon.
Yttrium-90-labeled monoclonal antibody for therapy: labeling by a new macrocyclic bifunctional chelating agent. (1990)

Yttrium-90 (90Y) is a promising radiometal for therapy of cancer due to its high-energy beta emission and a physical half-life of 2.67 days. Bifunctional chelating agents based on DTPA cyclic anhydride or EDTA do not form Y(III) complexes that are stable under physiologic conditions. A new macrocyclic bifunctional chelating agent based on 1,4,7,10-tetraazacylododecane-N,N',N",N"'-tetraacetic acid (DOTA) forms a stable Y(III) complex. It was converted to p-bromoacetamidobenzyl-DOTA (BAD), and conjugated to monoclonal antibody Lym-1 via 2-iminothiolane, either as the free ligand or as the 88Y chelate. Stability studies of Lym-1-2IT-BAD-88Y in human serum in vitro showed no measurable loss of Y(III) from the ligand over a 25-day period. In Raji-tumored mice, tumor uptake was 16.8% of the injected dose per gram of tissue on Day 3. The bone uptake was 2.0, 3.6, and 2.1% injected dose per gram of tissue on Day 1, 3, and 5, respectively. The biodistribution of the control 88Y-citrate demonstrated continuous increase in bone uptake from 13.8% injected dose per gram on Day 1 to 24.9% injected dose per gram on Day 4.
Regulation of neural stem cell differentiation in the forebrain (1998)

In the developing forebrain, mounting evidence suggests that neural stem cell proliferation and differentiation is regulated by growth factors. In vitro in the presence of serum, stem cell proliferation is predominantly mediated by fibroblast growth factor-2 (FGF-2) whereas neuronal differentiation can be triggered by FGF-1 in association with a specific heparan sulphate proteoglycan. On the other hand, astrocyte differentiation in vivo and in vitro appears to be dependent on signalling through the leukaemia inhibitory factor receptor (LIFR). The evidence suggests that in the absence of LIFR signalling, the stem cell population is present at approximately the same frequency and can generate neurons but is blocked from producing astrocytes that express glial fibrillary acidic protein (GFAP) or have trophic functions. The block can be overcome by other growth factors such as BMP-2/4 or interferon-gamma, providing further evidence that the inhibition to astrocyte development does not result from loss of a precursor population. Signalling through the LIFR, in addition to stimulating astrocyte differentiation, may also inhibit neuronal differentiation, which may explain why this receptor is expressed at the earliest stages of neurogenesis. Another signalling system which also exerts its influence on neurogenesis through active inhibition is Delta-Notch. We show in vitro that at high cell densities which impede neuronal production by FGF-1, lowering the levels of expression of the receptor Notch by antisense oligonucleotide results in a significant increase in neuronal production. Thus, stem cell differentiation appears to be dependent on the outcome of interactions between a number of signalling pathways, some which promote specific lineages and some which inhibit.
An Estimate of the Incidence of Depression in Idiopathic Parkinson's Disease (1992)

Estimates of the prevalence of depression in idiopathic Parkinson's disease vary, but have been greater than in most comparison groups. In a survey of patients with Parkinson's disease (N = 339), the prevalence of depression was 47%. A total of 326 cases were reviewed to estimate the incidence of depression from September 30, 1984, to July 31, 1989. Assessments of depression during both the prevalent and the incident periods were noted in 258 cases. There was no history of depression in 129 cases, and nine new cases occurred. The incidence rate was 1.86% per year and the cumulative risk was 8.6%. Published estimates of the incidence of depression in the general population are few. In one study, the annual incidence of depression in individuals older than 40 years was 0.17%. In another, the incidence of depression in individuals older than 50 years was 0.14% for men and 0.29% for women. Although our retrospective study probably underdiagnoses depression, the incidence of depression is increased in Parkinson's disease.
Strategies for engineering human chromosomes with therapeutic potential (2001)

Human engineered chromosomes (HECs) have several potential advantages over currently used vectors for gene therapy applications. Firstly, there is no upper size limit to DNA that can be cloned in these vectors. Secondly, their extrachromosomal nature ensures that introduced genes are neither disruptive to, nor affected by, the genome of the host cell. Finally, being solely human in origin, HEC vectors should not evoke adverse host immunogenic responses. Recent advances have produced a variety of HECs via several different approaches. This review focuses on the current methodologies for making HEC vectors, the advantages and problems associated with each strategy, and discusses the outlook for HEC vectors as ex vivo therapeutic agents.
Applications of Diglycolamide Based Solvent Extraction Processes in Spent Nuclear Fuel Reprocessing, Part 1: TODGA (2018)

Over the last decade there has been much interest in the applications of diglycolamide (DGA) ligands for the extraction of the trivalent lanthanide and actinide ions from PUREX high active raffinates or dissolved spent nuclear fuel. Of the DGAs, the N,N,N’,N’-tetraoctyldiglycolamide (TODGA) is the best known and most widely studied. A number of new actinide separation processes have been proposed based on extraction with TODGA. This review covers TODGA-based processes and extraction data, specifically focusing on how phase modifiers have been used to increase metal loading and thus enhance the operating process envelopes. Effects of third phase formation and the organic phase speciation are reviewed in this context. Relevant aspects of the extraction chemistry of important solvents (TODGA-modifier-diluent combinations) are described and their performances demonstrated by a consideration of the published flowsheet tests. It is seen that modifiers are successfully enabling the use of TODGA in actinide separation processes but to date the identification and testing of suitable modifiers has been rather empirical. There is a growing understanding of the fundamental chemistry occurring in the organic phase and how that affects extractant speciation and metal loading capacity but studies are still needed if TODGA-based flowsheets are to become an industrially deployable option for minor actinide (MA) recovery processes.
Bacterial Toxins Inhibiting or Activating Small GTP‐Binding Proteins (1999)

Amino acids located on the switch 1 or switch 2 domains of small GTPases of the Ras and Rho family are targets of several bacterial toxins. Exoenzyme C3 from Clostridium botulinum ADP-ribosylates specifically Rho at R43 and prevents the recruitment of Rho on the cell membrane. This blocks the downstream effects of the Rho GTPase. However, exoenzyme C3 is not a toxin, and chimeric proteins fusing C3 with the B moiety of either diphtheria toxin or Pseudomonas aeruginosa exotoxin A have been produced to intoxicate cells with low concentration of C3. C. difficile toxin B modifies by glucosylation Rho on T37 and Rac and Cdc42 on T35. Glucosylation of Rho, Rac, and Cdc42 blocks the binding of these GTPases on their downstream effectors. C. sordellii lethal toxin modifies Ras, Rap, and Rac on T35 by glucosylation. Cytotoxic necrotizing factor 1 (CNF1), from uropathogenic Escherichia coli strains, deamidates Q63 of Rho into E63, thereby blocking the intrinsic or GAP-mediated GTPase of Rho. This allows permanent activation of Rho. Thus, Rho GTPases are targets for three different toxin activities. Molecular mechanisms of these toxins are discussed.
Uptake and accumulation of the vital dye hydroethidine in neoplastic cells. (1986)

Hydroethidine, a reduced form of ethidium bromide, was used as a vital dye in fluorescence assays that allowed visual and semiquantitative monitoring of dye uptake and accumulation by fluorescence microscopy, flow cytometry, image analysis, and microfluorimetry. The excitation and emission filters were chosen to detect hydroethidine and exclude ethidium. Microscopically, there were differences in fluorescence intensities and fluorescence patterns among various tumor cell lines. The fluorescence pattern varied from homogeneous blue in the cytoplasm to blue plus brilliant packets of bluish-white distributed in the cytoplasm. Nuclear staining varied from brown to reddish orange fluorescence. These differences were confirmed by flow cytometry and image analysis. A preliminary survey of various tumors indicated that uptake and accumulation of hydroethidine were dependent on concentration of the dye, duration of cell exposure to the dye, and metabolic state of the cells. Microfluorimetry made possible monitoring of 96 samples in a microculture plate in 30 seconds; thus, this method allows large numbers of samples to be read, with a tremendous savings in time and reagents. The results obtained from the different techniques used were corroborative; therefore, any one of the above techniques may be used in an assay.
Selective modulation through the glucocorticoid receptor ameliorates muscle pathology in mdx mice (2013)

The over-expression of NF-κB signalling in both muscle and immune cells contribute to the pathology in dystrophic muscle. The anti-inflammatory properties of glucocorticoids, mediated predominantly through monomeric glucocorticoid receptor inhibition of transcription factors such as NF-κB (transrepression), are postulated to be an important mechanism for their beneficial effects in Duchenne muscular dystrophy. Chronic glucocorticoid therapy is associated with adverse effects on metabolism, growth, bone mineral density and the maintenance of muscle mass. These detrimental effects result from direct glucocorticoid receptor homodimer interactions with glucocorticoid response elements of the relevant genes. Compound A, a non-steroidal selective glucocorticoid receptor modulator, is capable of transrepression without transactivation. We confirm the in vitro NF-κB inhibitory activity of compound A in H-2K(b) -tsA58 mdx myoblasts and myotubes, and demonstrate improvements in disease phenotype of dystrophin deficient mdx mice. Compound A treatment in mdx mice from 18 days of post-natal age to 8 weeks of age increased the absolute and normalized forelimb and hindlimb grip strength, attenuated cathepsin-B enzyme activity (a surrogate marker for inflammation) in forelimb and hindlimb muscles, decreased serum creatine kinase levels and reduced IL-6, CCL2, IFNγ, TNF and IL-12p70 cytokine levels in gastrocnemius (GA) muscles. Compared with compound A, treatment with prednisolone, a classical glucocorticoid, in both wild-type and mdx mice was associated with reduced body weight, reduced GA, tibialis anterior and extensor digitorum longus muscle mass and shorter tibial lengths. Prednisolone increased osteopontin (Spp1) gene expression and osteopontin protein levels in the GA muscles of mdx mice and had less favourable effects on the expression of Foxo1, Foxo3, Fbxo32, Trim63, Mstn and Igf1 in GA muscles, as well as hepatic Igf1 in wild-type mice. In conclusion, selective glucocorticoid receptor modulation by compound A represents a potential therapeutic strategy to improve dystrophic pathology.
[Effects of stimulating periaqueductal gray on the nociceptive neuron discharges of post-thalamic nucleus evoked by stimulation of splanchnic nerve in cats]. (1991)

The effects of stimulating periaqueductal gray (PAG) on the nociceptive neuron discharges of pronucleus evoked by stimulating the splanchnic nerve in cats were studied. The two kinds of inhibitory action were observed. One was called early phase or prompt inhibition phase which occurred within 30 ms to 150 ms after stimulation of PAG. The other was called slow-pase or sustained inhibition which occurred from a few minutes to more than ten minutes after the stimulation of PAG. The results showed that PAG played an important role in the analgesia of visceral pain. Both kinds of inhibition may be blocked by naloxone, this suggests that endogenous opiate like substances involved in these inhibitory processes caused by stimulating role in the inhibitory effect of PAG.
Detection of DNA in single cells using an automated cell deposition unit and PCR. (1995)

A highly effective single-cell PCR method using a fluorescence-activated cell sorting (FACS)-based automated cell deposition unit (ACDU) that sorts single cells directly into PCR tubes was developed. To evaluate the sensitivity of this method, single ACH-2 cells (containing one HIV-1 genome per cell) were sorted, and 220 out of 228 samples (96.5%) were HIV DNA-positive by PCR. Furthermore, the number of samples accidentally containing more than one cell was determined by sorting single cells from a mixture of human cytomegalovirus (HCMV)-infected fibroblasts and ACH-2 cells. Multiplex nested PCR (nPCR) was then performed, detecting HCMV and HIV DNA simultaneously. From 66 sorted cells, 2 (3%) were double-positive for HIV and HCMV, 31 (47%) for HCMV alone, 30 (45.5%) for HIV alone and 3 (4.5%) were PCR-negative. The ACDU was then programmed to sort defined numbers of cells into PCR tubes. This is similar to classic dilution assays in that it allows the determination of the percentage of cells that was positive for a specific DNA. The accuracy of multiple cell deposition by the ACDU was evaluated by determining the percentage of HIV-positive cells in defined mixtures of ACH-2 and uninfected H9 cells. Infection rates determined by the ACDU correlated well with the rates expected from the given dilutions.
Coding of Two-Tone Images (1977)

We review the concepts and techniques of efficient coding for the transmission or storage of two-tone images, such as business documents and weather maps. Digitization considerations are presented first. Then we discuss in detail the basic concepts (both heuristic and mathematical) of efficient coding. This is followed by descriptions of typical coding techniques. Finally, channel errors and buffer requirements are discussed briefly.
Pharmacological Management of Huntingtons Disease: An Evidence- Based Review (2006)

There is poor evidence in management of HD today. The analysis of the twenty level-I studies fails to result in any treatment recommendation of clinical relevance. High-quality RCT are highly warranted to advance HD treatment in clinical practice.
Life on the edge: amazing creatures thriving in extreme environments (1998)

Of Extremists and Eccentrics: A Personal Preface Introduction: Life and Its Limits Things One Needs for a Living What Do We Mean by Normal after All? The Limits of Life on Earth Extreme Environments and Their Inhabitants Profile: Thomas Brock and the Discovery of the Hyperthermophiles Some Like It Hot: Life around Geysers and Volcanoes Stay Cool: Life at Subzero Temperatures Sidelines: Of Polar Bears and Penguins - Vertebrate Life at the Poles Living under Pressure: The Deep Sea Sidelines: On Diving A Light in the Dark: Luminescent Creatures of the Deep Sea Travel to the Center of the Earth: The Deep Subsurface as a Biotope Extra Dry: Survival in the Desert Saturated with Salt: The (Allegedly) Dead Sea as a Biotope Acid Heads and Basic Needs: Life at Extreme pH Nature's Eco-Brigade: Oil-Degrading Bacteria The Cell's Survival Kit The Heat Shock Response Sidelines: How to Hunt for Stress Proteins Heat Shock Proteins Acting as Molecular Chaperones Antifreeze and Cold Shock Proteins Focus: Structure and Function of the Heat Shock Protein GroEL Adaptations by Changes of Amino Acid Sequences Chemical Adaptations: Small Molecules Some New Tricks from the Cell's Repair Workshop Focus: The Growing Family of Photolyase Enzymes Sidelines: How Hot Love Helps Archaebacteria to Survive Waiting for Better Times: Sporulation as a Survival Strategy Focus: The Case of the Missing Alanine - a Biochemical Detective Story Two's Company: Symbiosis Helps Species to Spread in Hostile Environments Relevance of Extremes for Biotechnology and Medicine An Extremely Short History of Biotechnology Hyperthermophilic Enzymes Profile: Kary Mullis and the Polymerase Chain Reaction Preservation by Freezing and Freeze-Drying Profile: Pierre Douzou and the Invention of Cryoenzymology High-Pressure Biotechnology Bacteriorhodopsin as an Optoelectronic Component Extremophiles and Disease: Acid-Resistant Bacteria in the Stomach Medical Applications of Heat Shock Proteins {
Restrictions on Transversal Encoded Quantum Gate Sets (2009)

Transversal gates play an important role in the theory of fault-tolerant quantum computation due to their simplicity and robustness to noise. By definition, transversal operators do not couple physical subsystems within the same code block. Consequently, such operators do not spread errors within code blocks and are, therefore, fault tolerant. Nonetheless, other methods of ensuring fault tolerance are required, as it is invariably the case that some encoded gates cannot be implemented transversally. This observation has led to a long-standing conjecture that transversal encoded gate sets cannot be universal. Here we show that the ability of a quantum code to detect an arbitrary error on any single physical subsystem is incompatible with the existence of a universal, transversal encoded gate set for the code.
Thromboendarterectomy for Chronic, Major-Vessel Thromboembolic Pulmonary Hypertension (1987)

Since 1970, forty-two patients with pulmonary hypertension due to chronic, thromboembolic obstruction of the major pulmonary arteries have had pulmonary thromboendarterectomy at the University of California, San Diego, and the San Diego Veterans Medical Centers. Duration of symptoms before admission averaged 4.4 years, with many alternative diagnoses having been made. At admission, 29 patients had class IV disease by New York Heart Association criteria, and 12, class III. Immediately after surgery, pulmonary vascular resistance declined significantly (p < 0.001) from 897 ± 352 dynes/s · cm-5 to 278 ± 135 dynes/s · cm-5. Seven patients with class IV disease died in the postoperative period. Of the 35 survivors (mean follow-up, 28 months), 16 had class I disease; 18, class II; and 1, class III. Of the 17 patients who have returned for cardiac catheterization at 4 to 12 months after surgery, a further decline (p < 0.05) in pulmonary vascular resistance has occurred. This experience indicates that the disorder is commoner than we previously suspected and that thromboendarterectomy is feasible, even in patients with severe and protracted hemodynamic compromise.
Body composition of patients with malnutrition and cancer. Summary of methods of assessment (1985)

Body composition is determined, by multiple isotope dilution, to obtain an accurate and precise measure of the nutritional state and to evaluate the response to specialized nutritional therapy. Malnutrition results in a loss of body cell mass (BCM) accompanied by an expansion of the extracellular mass (ECM). Thus, in 75 malnourished patients the BCM was 40.5% less and the ECM was 24.6% greater than that of 25 normal volunteers, resulting in a body weight difference of only 16.3%. In 19 normally nourished patients undergoing major elective surgery, by the fifth postoperative day the BCM decreased by 13.9% and the ECM increased by 9.6%, resulting in a 3.9% loss of body weight. During an 18-month period, body composition was determined in 43 patients with cancer. Eighteen patients were nutritionally normal, whereas 25 were malnourished. In 17 of the malnourished patients, body composition was determined at 2-week intervals while they were receiving total parenteral nutrition (TPN). Body composition remained unchanged in nine but improved in eight, with a BCM increase from 14.6 +/- 1.1 to 18.4 +/- 1.2 kg. These data demonstrated that an improvement in the nutritional state can be achieved in patients with cancer.
Process execution controls as a mechanism to ensure consistency (1989)

A mechanism for ensuring that the changes to a system and its data occur in a consistent manner is presented. The mechanism, process execution controls, imposes restrictions on the method of access to the data, unlike access controls which impose restrictions upon which users can access the data. This mechanism imposes another layer to the currently existing access control restrictions, but one that is, for the most part, transparent to the user. Although transparent, the system offers the capability of containing viruses within a given domain. The author presents two methods of implementation; extending current access control lists and implementing complementary execution control lists.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Vaccinia virion protein VP8, the 25 kDa product of the L4R gene, binds single-stranded DNA and RNA with similar affinity (1997)

Vaccinia virus protein VP8 is a 25 kDa product of the L4R gene and is an abundant virion protein that binds single-stranded (ss) and double-stranded (ds) DNA. Binding of ssDNA is preferred at high salt concentrations. Using a recombinant 25 kDa L4R (rL4R) protein and a gel mobility shift assay with radiolabelled oligonucleotides, the Kd for a 45mer oligonucleotide was determined to be 2 nM. The Kd was unaltered by 50 mM KCl but was reduced 35-fold by 100 mM KCl. Multiple rL4R molecules bound to a single 45mer oligonucleotide, and using oligonucleotides of different lengths it was calculated that one rL4R molecule bound every 17 nt. Binding to ssDNA was competed by both deoxyribo- and ribo-polynucleotides. RNA binding was observed for both rL4R and native VP8, purified from virions, using a gel mobility shift with a radiolabelled ssRNA of 130 nt. The Kd of rL4R for this ssRNA substrate was 3 nM in the absence of salt and binding was positively cooperative. The potential roles of L4R protein in vaccinia virus early transcription are discussed.
Fragment size and level of cell-free DNA provide prognostic information in patients with advanced pancreatic cancer (2018)

This study demonstrates that cfDNA fragment size and cfDNA levels can be used to predict disease outcome in patients with advanced pancreatic cancer. The described approach, using a rapid, economic and simple test to reveal prognostic information, has potential for future treatment stratification and monitoring.