gebhart/patrepeval huggingface dataset:
Probing the Relation Between Force—Lifetime—and Chemistry in Single Molecular Bonds (2001)

On laboratory time scales, the energy landscape of a weak bond along a dissociation pathway is fully explored through Brownian-thermal excitations, and energy barriers become encoded in a dissociation time that varies with applied force. Probed with ramps of force over an enormous range of rates (force/time), this kinetic profile is transformed into a dynamic spectrum of bond rupture force as a function of loading rate. On a logarithmic scale in loading rate, the force spectrum provides an easy-to-read map of the prominent energy barriers traversed along the force-driven pathway and exposes the differences in energy between barriers. In this way, the method of dynamic force spectroscopy (DFS) is being used to probe the complex relation between force-lifetime-and chemistry in single molecular bonds. Most important, DFS probes the inner world of molecular interactions to reveal barriers that are difficult or impossible to detect in assays of near equilibrium dissociation but that determine bond lifetime and strength under rapid detachment. To use an ultrasensitive force probe as a spectroscopic tool, we need to understand the physics of bond dissociation under force, the impact of experimental technique on the measurement of detachment force (bond strength), the consequences of complex interactions in macromolecular bonds, and effects of multiply-bonded attachments.
The Stress—Strain Characteristics of Animal Fibers After Reduction and Alkylation (1965)

Animal fibers were reduced to varying degrees with solutions of thiols and alkylated with methyl iodide or ethylene dibromide. The stress-strain curves of S-methylated Lincoln wool fibers showed the following characteristics. The stresses at the end of the Hookean region and yield region and the breaking stress approached zero at zero disulfide content and maintained a constant ratio. Likewise the slopes of the yield and post-yield region showed a constant ratio and extrapolated to zero at zero disulfide content. The decrease in stress or slope per disulfide bond broken was much greater at low disulfide contents than at high disulfide contents. The strains at the end of the yield region and at break increased with decreasing disulfide content and the effect of each disulfide broken was greatest at low disulfide contents. The relationship between strain at the end of the yield region and residual disulfide content was the same, within experimental error, for all fiber types. Reduction followed by reaction with ethylene dibromide did not greatly affect the stress-strain properties of the fibers. Reduction without subsequent alkylation, how ever, decreased the stiffness of the fibers much more than the rupture of an equal number of disulfide bonds by reduction and methylation. It is concluded that side-chain interactions between helical structures and matrix molecules containing many intrachain disulfide bonds are chiefly responsible for stiffen ing the fiber in the Hookean region. The yield and post-yield regions also are con sidered in terms of interactions between microfibrils and matrix, particularly with respect to the effects of disulfide bonds linking proteins in the two phases.
Whittemore's Science and Practice of Pig Production (2006)

Preface and Acknowledgements. Contributors. Chapter 1 Introduction. Chapter 2 Pig meat and carcass quality. Chapter 3 Growth and body composition changes in pigs. Chapter 4 Reproduction. Chapter 5 Pig behaviour and welfare. Chapter 6 Development and improvement of pigs by genetic selection. Chapter 7 The maintenance of health. Chapter 8 Energy value of feedstuffs for pigs. Chapter 9 Nutritional value of proteins and amino acids in feedstuffs for pigs. Chapter 10 Value of fats and oils in pig diets. Chapter 11 Energy and protein requirements for maintenance, growth and reproduction. Chapter 12 Requirements for water, minerals and vitamins. Chapter 13 Appetite and voluntary feed intake. Chapter 14 Diet formulation. Chapter 15 Optimisation of feed supply to growing pigs and breeding sows. Chapter 16 Product marketing. Chapter 17 Environmental management of pigs. Chapter 18 Production performance monitoring. Chapter 19 Simulation modelling. Chapter 20 Conclusion. Appendices. Index
A G Protein Directly Regulates Mammalian Cardiac Calcium Channels (1987)

A possible direct effect of guanine nucleotide binding (G) proteins on calcium channels was examined in membrane patches excised from guinea pig cardiac myocytes and bovine cardiac sarcolemmal vesicles incorporated into planar lipid bilayers. The guanosine triphosphate analog, GTP gamma S, prolonged the survival of excised calcium channels independently of the presence of adenosine 3',5'-monophosphate (cAMP), adenosine triphosphate, cAMP-activated protein kinase, and the protein kinase C activator tetradecanoyl phorbol acetate. A specific G protein, activated Gs, or its alpha subunit, purified from the plasma membranes of human erythrocytes, prolonged the survival of excised channels and stimulated the activity of incorporated channels. Thus, in addition to regulating calcium channels indirectly through activation of cytoplasmic kinases, G proteins can regulate calcium channels directly. Since they also directly regulate a subset of potassium channels, G proteins are now known to directly gate two classes of membrane ion channels.
Asymmetric strain in nanoscale patterned strained-Si/strained-Ge/strained-Si heterostructures on insulator (2007)

The engineering of asymmetric strain is demonstrated in nanoscale patterned strained-Si/strained-Ge/strained-Si heterostructure on insulator with body thickness of 15nm. Starting material has layers with symmetric in-plane strain, including biaxial strained Si (∼1.8%, tension) and biaxial strained Ge (∼1.8%, compression). Micro-Raman spectroscopy is utilized to characterize the stress in heterostructures patterned into 10-μm-long bars with widths ranging from 300to30nm. Raman measurements are consistent with the transformation from biaxial to uniaxial compressive strain in the Ge for 30-nm-wide bars, as predicated by simulations. Measurements also demonstrate enhanced asymmetric relaxation in the tensile strained Si cap as its thickness is increased.
Inhibition of Histone Deacetylation Does Not Block Resilencing of p16 after 5-Aza-2′-Deoxycytidine Treatment (2007)

Epigenetic drugs are in use in clinical trials of various human cancers and are potent at reactivating genes silenced by DNA methylation and chromatin modifications. We report here the analysis of a set of normal fibroblast and cancer cell lines after combination treatment with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5-aza-CdR) and the histone deacetylase inhibitor 4-phenylbutyric acid (PBA). Low doses of the drug combination caused cell cycle arrest, whereas high doses induced apoptosis in T24 bladder carcinoma cells. Both p16 (CDKN2A/INK4) and p21 (CIP1/SDI1/WAF1) expression were induced to similar levels in normal and cancer cells in a dose-dependent fashion after combination treatments. We detected a distinct increase of histone H3 acetylation at lysine 9/14 near the transcription start sites, in both LD419 normal fibroblasts and T24 bladder carcinoma cells, whereas the acetylation changes in the p21 locus were less apparent. Interestingly, the levels of trimethylation of histone H3 on lysine 9, which usually marks inactive chromatin regions and was associated with the p16 promoter in silenced T24 cells, did not change after drug treatments. Furthermore, we provide evidence that the remethylation of the p16 promoter CpG island in T24 cells after 5-aza-CdR treatment cannot be halted by subsequent continuous PBA treatment. The p16 gene is resilenced with kinetics similar to 5-aza-CdR only-treated cells, which is also marked by a localized loss of histone acetylation at the transcription start site. Altogether, our data provide new insights into the mechanism of epigenetic drugs and have important implications for epigenetic therapy.
Most of the homeobox-containing Xhox 36 transcripts in early Xenopus embryos cannot encode a homeodomain protein. (1990)

Multiple Xhox 36 transcripts accumulate in Xenopus embryos from gastrula to early tadpole stages. The transcripts were characterized by sequencing cDNA clones and by S1 protection and Northern (RNA) blotting of embryonic RNA with probes derived from the cDNAs. The Xhox 36 RNAs included unspliced precursor transcripts that accumulated in the embryonic nuclei, spliced transcripts that contained multiple stop codons in frame with the homeobox, and less abundant coding mRNAs. These transcripts were generated either by alternative splicing or multiple initiations from a single Xhox 36 gene. The sequence of a cDNA clone of the unspliced transcript showed that the intron contained a noncanonical 3' splice site. However, the intron was spliced efficiently when expressed from a plasmid injected into Xenopus embryos, suggesting that the inefficient splicing of the endogenous RNA is not due to the unusual 3' splice site. The accumulation of noncoding and unspliced transcripts suggests multiple levels of regulation in the embryonic expression of the Xhox 36 gene.
High levels of engraftment with a single infusion of bone marrow cells into normal unprepared mice. (1995)

Repetitive infusion of 40 million male murine marrow cells (total 200 million cells) into normal unprepared female BALB/c hosts for 5 consecutive days results in high levels of engraftment at 1-25 months postinfusion, as determined by Southern blot analysis using a Y chromosome-specific probe. We investigated the importance of the schedule of injections in this engraftment model. Surprisingly, a single infusion of 200 x 10(6) male BALB/c bone marrow cells analyzed at 7-14 weeks postinfusion resulted in engraftment levels in individual female mice of over 50% with mean values of 25 +/- 2% for 44 individual transplant points. Engraftment levels in spleen and thymus were 14 +/- 1% and 18 +/- 3%, respectively. Including heparin in the infusion increased engraftment in marrow, spleen, and thymus. Administration of the cells over five or 10 separate infusions, rather than in one injection, did not increase engraftment levels. If the infused bone marrow cells seeded equally between host spleen, thymus, and bone marrow, and if all cells engrafted, the bone marrow engraftment seen here approaches the theoretical maximum. This suggests either a large number of available "niches" or the displacement of host marrow cells by infused marrow. The latter possibility is upheld by cell counts per tibia/femur and total seven-factor HPP-CFC/tibia, which were not increased. These data suggest that a single infusion of marrow homes quantitatively to spleen, thymus, and bone marrow, possibly displacing host cells in the process.
ASSISTED PROTEIN FOLDING (1999)

The classical experiments by Anfinsen and others established that the entire information required for the folding of polypeptide chains to the native three-dimensional conformation is encoded in their primary amino acid sequences (Epstein et al., 1963). This information directs the formation of multiple non-covalent and covalent interactions within polypeptide chains and between subunits of protein oligomers which drive the folding process and stabilize the folded structures (chapter Seckler and Jaenicke). It also establishes a balance between structural stability and flexibility, achieved by low conformational stability of the folded protein (Privalov, 1979), which is required for the folding process itself and the activity of the folded protein. This balance implies that correct and incorrect folding, as well as native and nonnative structures, are separated by only relatively small energy barriers. Subtle changes in the amino acid sequence or the folding milieu may therefore have dramatic consequences for the folding process and the structural integrity of proteins. Misfolding of proteins is indeed the major damaging consequence of stress situations such as heat shock. Misfolded proteins frequently expose hydrophobic surfaces that are prone to intermolecular aggregation, a largely irreversible reaction.
Positive co‐regulation of the Escherichia coli carnitine pathway cai and fix operons by CRP and the CaiF activator (1999)

Activation of the two divergent Escherichia coli cai and fix operons involved in anaerobic carnitine metabolism is co-dependent on the cyclic AMP receptor protein (CRP) and on CaiF, the specific carnitine-sensitive transcriptional regulator. CaiF was overproduced using a phage T7 system, purified on a heparin column and ran as a 15 kDa protein on SDS-PAGE. DNase I footprinting and interference experiments identified two sites, F1 and F2, with apparently comparable affinities for the binding of CaiF in the cai-fix regulatory region. These sites share a common perfect inverted repeat comprising two 11 bp half-sites separated by 13 bp, and centred at -70 and -127 from the fix transcription start site. They were found to overlap the two low-affinity binding sites, CRP2 and CRP3, determined previously for CRP. Gel shift assays and footprinting experiments suggest that CaiF and CRP bind co-operatively to the F1/CRP2 and F2/CRP3 sites of the intergenic cai-fix region. Moreover, they appeared to serve the simultaneous binding of each other, giving rise to an original multiprotein CRP-CaiF complex enabling RNA polymerase recruitment and local DNA untwisting, at least at the fix promoter. Using random mutagenesis, two CaiF mutants impaired in transcription activation were isolated. The N-terminal A27V mutation affected the structural organization of the activator, whereas the central I62N mutation was suggested to interfere with DNA binding.
Synergism between cisplatin and topoisomerase I inhibitors, NB-506 and SN-38, in human small cell lung cancer cells. (1996)

Topoisomerase I-targeting anticancer agents such as 7-ethyl-10-[4-(1-piperidyl)-1-piperidyl]carbonyloxy-camptothecin (CPT-11) and 6-N-formylamino-12,13-dihydro-1,11-dihydroxy-13-(beta-D- glucopyranosyl)-5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-di one (NB-506) have been developed and show strong antitumor activity against various cancers. We examined the interaction of these drugs and cisplatin (CDDP), and biochemical mechanisms of synergism between them. Interaction of drugs in human small cell lung cancer cells, SBC-3, was analyzed using the isobologram method. Combinations of CDDP with NB-506, CPT-11, and an active metabolite of CPT-11, 7-ethyl-10-hydroxy-CPT (SN-38), showed synergistic effects. Formation of DNA interstrand cross-links (ICLs) on the cells was analyzed using an alkaline elution assay and increased ICLs were observed by simultaneous exposure to CDDP (1.5 microM) and NB-506 (10 nM) compared with that in response to CDDP alone. DNA repair after ICL formation induced by 3-h exposure to CDDP (1.5 microM) was reduced by NB-506 (10 nM) exposure. On the other hand, a higher concentration of CDDP (150 microM) enhanced the topoisomerase I inhibitory activity of NB-506 and SN-38 determined by relaxation of supercoiled Escherichia coli DNA. These biological interactions might result in synergistic interactions between CDDP and NB-506 or SN-38. Topoisomerase I inhibitors and CDDP may be a key regimen for cancer chemotherapy and merit further examination.
Mechanisms of analgesia by gabapentin and pregabalin – Calcium channel α2-δ [Cavα2-δ] ligands (2009)

CpTaylor Consulting, Chelsea, MI 48118, USA *Tel.: +1 734 475 2172. E-mail address:[email protected]
A reconfigurable approach to a systolic sorting architecture (2003)

A different approach to reconfigurable systolic arrays is described. In addition to making the interconnection network reconfigurable (to match the topology of the Algorithm flow graph), the authors make the individual processing elements themselves configurable, in order to provide the best match to the computational requirements of individual nodes. Rather than having a fixed instruction set, they hope to tailor the architecture of the different processing elements in such a way as to carry out their functions without the use of instruction streams. This reduces the problems of control and coordination and provides a closer match to the algorithm being implemented. The prototype architecture being developed and an analysis of its application to a particular class of problems (numeric sorting) are described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
PVT-Aware Leakage Reduction for On-Die Caches With Improved Read Stability (2005)

Effectiveness of previous SRAM leakage reduction techniques vary significantly as the leakage variation gets worse with process and temperature fluctuation. This paper proposes a simple circuit technique that adaptively trades off overhead energy for maximum leakage savings under severe leakage variations. The proposed run-time leakage reduction technique for on-die SRAM caches considers architectural access behavior to determine how often the SRAM blocks should enter a sleep mode. A self-decay circuit generates a periodic sleep pulse with an adaptive pulse period, which puts the SRAM array into a sleep mode more frequently at high leakage conditions (fast process, high temperature) and vice versa. An 0.18-/spl mu/m 1.8-V 16-kbyte SRAM testchip shows 94.2% reduction in SRAM cell leakage at a performance penalty less than 2%. Measurement results also indicate that our proposed memory cell improves SRAM static noise margin by 25%.
Pharmacophore Fingerprinting. 2. Application to Primary Library Design (1999)

A methodology for pharmacophore fingerprinting (PharmPrint), previously described in the context of QSAR, has been used to address the issues involved in primary library design. A subset of the MDDR (MDDR9104) has been used to define a reference set of bioactive molecules. A statistic has been devised to measure the discriminating power of molecular descriptors using the target class assignments for this set, for which the PharmPrint fingerprint outperformed other descriptors. A principal components analysis (PCA) of the fingerprints for the MDDR9104 produces a low dimensional representation within which molecular properties and other libraries can be visualized and explored. PCA calculations on subsets of classes show that this space is robust to the addition of new classes, suggesting that pharmacophoric space is finite and rapidly converging. We demonstrate the application of the PharmPrint methodology to the analysis and design of virtual combinatorial libraries using common scaffolds and building blocks.
Versorgung großer Rotatorenmanschettenrupturen (1999)

Es bleibt immer noch unklar, welche Rotatorenmanschettenrupturen als sog. große globale oder massive Rupturen zu klassifizieren sind. Sieht man sich die Literatur an, so erkennt man, daß die Einteilung der Rotatorenmanschettenrupturen größenmäßig zugeordnet wird, wobei die Klassifikation von Cofield massive oder große Rupturen als solche definiert, die einen Durchmesser von mehr als 5 cm haben. Dieses entspricht in der Klassifikation von Walch und Gschwend einer Ruptur Typ III, wobei hier noch die Bizepssehne mit in Betracht gezogen wird. Ein anderer Weg der Klassifikation ist die auch von uns vorgeschlagene funktionelle Einteilung der Rotatorenmanschettenrisse in Muskeleinheiten -, also solche, die den Supraspinatus/Infraspinatus betreffen als Zweisehnenruptur -, ist der Subscapularis mitbetroffen als Dreisehnenruptur. Globale Rupturen sind solche, in denen eine Rotatorenmanschette nicht mehr erkennbar ist, sondern, ähnlich einem Haarkranz, nur noch Gewebe in den lateralen und dorsalen Anteilen am Kopf adhärent sind, also Teres minor bzw.
A computational approach for genome-wide mapping of splicing factor binding sites (2009)

Alternative splicing is regulated by splicing factors that serve as positive or negative effectors, interacting with regulatory elements along exons and introns. Here we present a novel computational method for genome-wide mapping of splicing factor binding sites that considers both the genomic environment and the evolutionary conservation of the regulatory elements. The method was applied to study the regulation of different alternative splicing events, uncovering an interesting network of interactions among splicing factors.
Obesity Modulates the Association among APOE Genotype, Insulin, and Glucose in Men (2003)

Obesity modulates the association between the APOE genotype and fasting insulin and glucose levels in men. Although weight control is important in all people, it may be especially important in APOE4 men to modify potentially elevated fasting insulin and glucose levels.
CEACAM1, a Novel Serum Biomarker for Pancreatic Cancer (2007)

CEACAM1 is expressed in pancreatic adenocarcinoma, and serum levels of CEACAM1 serve as a useful indicator for the presence of pancreatic cancer. Additional validation studies on the use of serum CEACAM1 as a diagnostic marker in pancreatic cancer are warranted.
Apoptosis in serum of patients with solid tumours. (1999)

Apoptosis, which occurs in highly proliferating tumours spontaneously or during anticancer therapy, many lead to an elevated concentration of circulating nucleosomes in blood. In order to quantify the concentration of nucleosomes, we used the Cell Death Detectionplus-ELISA (CDDE) (Boehringer Mannheim, Germany) based on antibodies against histone and DNA, adapted it to the demands of liquid materials and standardized test performance and handling of serum. Furthermore, we investigated serum samples of 185 patients with solid tumours (additionally 24, treated with radio- or chemotherapy), 30 with acute inflammations and 50 healthy persons. Many patients with tumours (78%) and inflammations (77%) showed higher concentrations of serum-nucleosomes (> 100 AU), whereas 96% of all healthy persons had low values (< 100 AU). Follow up-studies revealed an early peak after initiation of therapy and correlated to the clinical outcome. The concentration of nucleosomes is a sensitive marker of cell death and could be used for monitoring the efficacy of antitumour therapy.
Oral Administration of Micronized Progesterone: A Review and More Experience (1996)

Historically, oral progesterone has been regarded clinically ineffective because of its poor absorption and rapid clearance. Recent evidence suggests that an oral micronized form of natural progesterone is readily absorbed, produces luteal phase serum concentrations, provokes an end-organ response, and has no detrimental effect on the lipoprotein profile. Thus it is considered by many to be an attractive alternative to synthetic progestin. We evaluated the effects of a single oral dose of micronized progesterone 300 mg in eight healthy postmenopausal women. The maximum serum concentration ranged from 15.72-625.98 ng/ml. The extent of absorption increased with increasing age. The reviewed literature and our data indicate considerable intersubject variability in the extent of progesterone absorbed after administration of oral micronized progesterone.
Primary Sjögren's syndrome in men (2008)

Although pSS is typically a disease affecting women, clinicians should be aware that it may be diagnosed in male patients. Except for haematological presentation, we could not find any notable differences in clinical and immunological characteristics between male and female patients with pSS.
The RNA World: Functional Diversity in a Nucleoside by Carboxyamidation of Uridine (1996)

Abstract A facile method for the 5-carboxyamidation of protected uridines is described allowing synthesis of an array of uridines with diverse functionality.