gebhart/patrepeval huggingface dataset:
Helium ion microscope invasiveness and imaging study for semiconductor applications (2007)

The helium ion gas field ion source is a novel charged particle source technology with potentially greater capabilities than electron beam based tools for imaging and nanomachining [Ward et al., J. Vac. Sci. Technol. B (to be published); Morgan et al., Microscopy Today 14, 24 (2006); V. N. Tondare, J. Vac. Sci. Technol. A 23, 1498 (2005)]. Potential strengths of He ions over electrons (scanning electron microscopy) are improved thin film surface sensitivity, material contrast, IBIC voltage contrast, Rutherford backscattering material contrast, and the ability to utilize in situ electron charge neutralization on floating substrates which have enhanced charging properties (e.g., masks, photoresist). In this article, the authors will discuss and illustrate examples highlighting several of these attributes. Helium ions, unlike electrons, induce collision events in the material lattice. A critical area to understand is the operating conditions and sample types for which the advantages of helium ion imaging can be realized. Dose, beam current, acceleration voltage, and material interaction are all key areas for modeling and empirical analysis to determine potential invasiveness. The focus of the study presented in this article relates to analyzing the potential lattice damage induced in silicon substrate for ion doses ranging from 1×1014to5×1015ions∕cm2. This range represents relatively light dose (fast scan) to intermediate dose (slow scan) imaging applications. Findings for doses in this range (as typically used in image applications) show little to no damage to the silicon lattice. This finding also agrees with SRIM [Ziegler et al., The Stopping and Ranges of Ions in Solids (Pergamon, New York, 1985), Vol. 1] Monte Carlo simulations, which predict that helium ion induced defect densities to be 4×1017to4×1018dis∕cm3. However, it is clear that with higher doses, defect densities will increase to a level that may be invasive to device structures (e.g., metal oxide semiconductor field effect transistor channels or gate oxides).
Indazole derivatives: the synthesis of various amino- and hydroxy-indazoles and derived sulphonic acids (1955)

R. R. Davies, J. Chem. Soc., 1955, 2412 DOI: 10.1039/JR9550002412
Gene Targeting (2000)

This chapter covers: Targeting DNA into cells Recombinant and repair enzymes in targeting Gene disruption and replacement
Quantitative analysis of Tn10Tet repressor binding to complete set oftetoperator mutants (1990)

A saturating oligonucleotide-directed mutagenesis of both tet operators in the tet regulatory sequence was performed yielding mutants with four identical base pair exchanges at equivalent positions in the four tet operator half sides. The mutants were cloned between bipolar lacZ and galK indicator genes on a multicopy plasmid allowing the quantitative analysis of their effects in vivo. In the absence of Tet repressor the mutations lead to considerably different expression levels of both genes. They are discussed with respect to the promoter consensus sequences. In particular, the -10 region of the in vivo active tetPR2 promoter is unambiguously defined by these results. In the presence of Tet repressor most of the mutants exhibit a lower affinity for that protein as determined quantitatively by their reduced expression levels. In general, tet operator recognition is most strongly affected by alterations of base pairs near the center of the palindromic sequence. The most important position is the third base pair, followed by base pairs two, four, five and six, the latter showing similar effects as base pair one. At each position, the four possible base pairs show different affinities for Tet repressor. They are discussed according to their exposure of H-bond donors and -acceptors in the major and minor grooves of the B-DNA. The results are in agreement with major groove contacts at positions two, three and five. At position four a low potential correlation of efficiencies with the H-bonding in the minor groove is found, while mutations at position six seem to influence repressor binding by other mechanisms.
Double-blind comparison of glucametacin and ketoprofen in chronic arthropathies (1983)

A new, non-steroidal anti-inflammatory agent, glucametacin, was compared with ketoprofen in a double-blind, crossover trial. The drugs were given in total daily doses of 420 mg glucametacin and 300 mg ketoprofen for 20 days to 30 patients with chronic arthropathies of an inflammatory or degenerative nature. Both drugs were well tolerated and resulted in significant improvements in a number of criteria of disease assessment. Although there were no significant differences between results seen with the two drugs, there appeared to be trends in favour of glucametacin in respect to both efficacy and tolerance.
Phase 3, randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of erenumab (amg 334) in migraine prevention: primary results of the strive trial (2017)

<h3>Objectives</h3> To evaluate the efficacy and safety/tolerability of erenumab (AMG 334) in a phase 3 trial of subjects with episodic migraine (EM) (NCT02456740). <h3>Methods</h3> In this multinational, double-blind, placebo-controlled trial, adults with EM (n=955) were randomised 1:1:1 to subcutaneous monthly placebo or erenumab 70 mg or 140 mg for 24 weeks. The primary endpoint was change from baseline in mean monthly migraine days (MMDs) over weeks 13-24. Secondary endpoints were ≥50% reduction in MMDs; change in mean acute migraine-specific medication days; change in mean Physical Impairment (PI) and Impact on Everyday Activities (EA) scores (as measured by the Migraine Physical Function Impact Diary (MPFID)). P-values for pairwise comparisons of each erenumab dose with placebo are presented. Statistical significance was determined after adjustment for multiple comparisons. <h3>Results</h3> Subjects reported 8.3 MMDs at baseline and experienced −3.2, −3.7, and −1.8 day reductions in the 70 mg, 140 mg and placebo groups, respectively (p&lt;0.001 for both). A≥50% reduction in MMDs was achieved by 43%, 50% and 27% in the 70 mg, 140 mg and placebo groups (p&lt;0.001 for both), and monthly acute migraine-specific medication days were reduced by −1.1, −1.6 and −0.2 days (p&lt;0.001 for both). Subjects had improved PI scores (−4.2, −4.8, −2.4 points in the 70 mg, 140 mg and placebo groups; p&lt;0.001) and EA scores (−5.5, −5.9 and −3.3 points; p&lt;0.001). The safety/tolerability profile of erenumab was similar to placebo; subjects most frequently reported nasopharyngitis, upper-respiratory-tract infection, and sinusitis. <h3>Conclusions</h3> Erenumab 70 mg and 140 mg significantly reduced migraine frequency and use of migraine-specific medications, reducing migraine’s impact on physical impairment and EA compared with placebo in this EM trial. Numerically greater efficacy was observed for the 140 mg dose consistently across all endpoints.
Transgenic mice demonstrate AP-1 (activator protein-1) transactivation is required for tumor promotion (1999)

Activator protein-1 (AP-1) is a transcription factor that consists of either a Jun-Jun homodimer or a Jun-Fos heterodimer. Transactivation of AP-1 is required for tumor promoter-induced transformation in mouse epidermal JB6 cells and for progression in mouse and human keratinocytes. Until now, the question of whether AP-1 transactivation is required for carcinogenesis in vivo has remained unanswered, as has the issue of functionally significant target genes. To address these issues we have generated a transgenic mouse in which transactivation mutant c-jun (TAM67), under the control of the human keratin-14 promoter, is expressed specifically in the basal cells of the epidermis where tumor induction is initiated. The keratin-14-TAM67 transgene was expressed in the epidermis, tongue, and cervix, with no apparent abnormalities in any tissue or organ. TAM67 expression blocked 12-O-tetradecanoylphorbol 13-acetate (TPA, phorbol 12-tetradecanoate 13-acetate) induction of the AP-1-regulated luciferase in AP-1 luciferase/TAM67 mice, but did not inhibit induction of candidate AP-1 target genes, collagenase-1 or stromelysin-3. More interestingly, TAM67 expression did not inhibit TPA-induced hyperproliferation. In two-stage skin carcinogenesis experiments, the transgenic animals showed a dramatic inhibition of papilloma induction. We conclude that transactivation of a subset of AP-1-dependent genes is required for tumor promotion and may be targeted for cancer prevention.
Therapeutic potential of nitric oxide donors in the prevention and treatment of atherosclerosis (2005)

Well-known risk factors for atherosclerosis include hypercholesterolaemia, hypertension, diabetes, and smoking. These conditions are associated with endothelial dysfunction, which itself is associated with reduced endothelial generation of nitric oxide (NO). This is an overview of the implications of NO generation in atherosclerosis and of the potential therapeutic benefit of drugs which donate NO, such as organic nitrates, nicorandil, and sydnonimines, or those which increase the availability of endogenous NO, such as statins, angiotensin-converting enzyme inhibitors, L-arginine, and tetrahydrobiopterin.
Histone Deacetylase Inhibitors: Inducers of Differentiation or Apoptosis of Transformed Cells (2000)

Histone deacetylase (HDAC) inhibitors have been shown to be potent inducers of growth arrest, differentiation, and/or apoptotic cell death of transformed cells in vitro and in vivo. One class of HDAC inhibitors, hydroxamic acid-based hybrid polar compounds (HPCs), induce differentiation at micromolar or lower concentrations. Studies (x-ray crystallographic) showed that the catalytic site of HDAC has a tubular structure with a zinc atom at its base and that these HDAC inhibitors, such as suberoylanilide hydroxamic acid and trichostatin A, fit into this structure with the hydroxamic moiety of the inhibitor binding to the zinc. HDAC inhibitors cause acetylated histones to accumulate in both tumor and normal tissues, and this accumulation can be used as a marker of the biologic activity of the HDAC inhibitors. Hydroxamic acid-based HPCs act selectively to inhibit tumor cell growth at levels that have little or no toxicity for normal cells. These compounds also act selectively on gene expression, altering the expression of only about 2% of the genes expressed in cultured tumor cells. In general, chromatin fractions enriched in actively transcribed genes are also enriched in highly acetylated core histones, whereas silent genes are associated with nucleosomes with a low level of acetylation. However, HDACs can also acetylate proteins other than histones in nucleosomes. The role that these other targets play in the induction of cell growth arrest, differentiation, and/or apoptotic cell death has not been determined. Our working hypothesis is that inhibition of HDAC activity leads to the modulation of expression of a specific set of genes that, in turn, result in growth arrest, differentiation, and/or apoptotic cell death. The hydroxamic acid-based HPCs are potentially effective agents for cancer therapy and, possibly, cancer chemoprevention.
An Analysis of Three Transaction Processing Architectures (1988)

In this paper, we investigate the issues involved in using multiprocessors for high performance transaction processing applications. We use a simulation model to compare the performance of three different architectures, namely, Shared Everything, Shared Nothing and Shared Disks. In Shared Everything, any processor can access any disk and all memory is shared. In Shared Nothing, neither disks nor memory is shared. In Shared Disks, any processor can access any disk, but each has its own private main memory. We first study four different variations of the Shared Disks architecture which attempt to minimize lock request messages. We will then compare the best Shared Disks variation with Shared Nothing and Shared Everything. In addition, we study how intraquery parallelism affects the performance of the architectures.
Algorithm of OMA for large-scale orthology inference (2008)

OMA contains several novel improvement ideas for orthology inference and provides a unique dataset of large-scale orthology assignments.
The von Willebrand factor–reducing activity of thrombospondin-1 is located in the calcium-binding/C-terminal sequence and requires a free thiol at position 974 (2002)

Plasma von Willebrand factor (VWF) is a multimeric protein that mediates adhesion of platelets to sites of vascular injury; however, only the very large VWF multimers are effective in promoting platelet adhesion in flowing blood. The multimeric size of VWF can be controlled by the glycoprotein, thrombospondin-1 (TSP-1), which facilitates reduction of the disulfide bonds that hold VWF multimers together. The TSP family of extracellular glycoproteins consists of 5 members in vertebrates, TSP-1 through TSP-4 and TSP-5/COMP. TSP-1 and TSP-2 are structurally similar trimeric proteins composed of disulfide-linked 150-kDa monomers. Recombinant pieces of TSP-1 and TSP-2 incorporating combinations of domains that span the entire subunit were produced in insect cells and examined for VWF reductase activity. VWF reductase activity was present in the Ca(++)-binding repeats and C-terminal sequence of TSP-1, but not of TSP-2. Alkylation of Cys974 in the C-terminal TSP-1 construct, which is a serine in TSP-2, ablated VWF reductase activity. These results imply that the reductase function of TSP-1 centers around Cys974 in the C-terminal sequence.
A Systematic Literature Review of Neuroimaging of Psychopathic Traits (2020)

Structural and functional aberrancies involving the limbic and paralimbic systems including reduced integrity of the uncinate fasciculus appear to be associated with core psychopathic features. Furthermore, this review points towards the idea that ASPD and psychopathy might stem from divergent biological processes.
Reactive Polymer Coatings that “Click” (2006)

Everything just clicks into place: Alkyne-group functionalized polymer films that are deposited from the gas phase allow spatially defined immobilization of biomolecules, such as biotin, through the 1,3-dipolar cycloaddition click reaction with azide derivatives (see scheme). Such biofunctional surfaces have applications in diagnostics and biosensors. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2006/z600357_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Clinical applications of mesenchymal stem cells (2012)

Mesenchymal stem cells (MSC) have generated a great amount of enthusiasm over the past decade as a novel therapeutic paradigm for a variety of diseases. Currently, MSC based clinical trials have been conducted for at least 12 kinds of pathological conditions, with many completed trials demonstrating the safety and efficacy. This review provides an overview of the recent clinical findings related to MSC therapeutic effects. Roles of MSCs in clinical trials conducted to treat graft-versus-host-disease (GVHD) and cardiovascular diseases are highlighted. Clinical application of MSC are mainly attributed to their important four biological properties- the ability to home to sites of inflammation following tissue injury when injected intravenously; to differentiate into various cell types; to secrete multiple bioactive molecules capable of stimulating recovery of injured cells and inhibiting inflammation and to perform immunomodulatory functions. Here, we will discuss these four properties. Moreover, the issues surrounding clinical grade MSCs and principles for MSC therapeutic approaches are also addressed on the transition of MSCs therapy from bench side to bedside.
User‐adaptive control of a magnetorheological prosthetic knee (2003)

A magnetorheological knee prosthesis is presented that automatically adapts knee damping to the gait of the amputee using only local sensing of knee force, torque, and position. To assess the clinical effects of the user‐adaptive knee prosthesis, kinematic gait data were collected on four unilateral trans‐femoral amputees. Using the user‐adaptive knee and a conventional, non‐adaptive knee, gait kinematics were evaluated on both affected and unaffected sides. Results were compared to the kinematics of 12 age, weight and height matched normals. We find that the user‐adaptive knee successfully controls early stance damping, enabling amputee to undergo biologically‐realistic, early stance knee flexion. These results indicate that a user‐adaptive control scheme and local mechanical sensing are all that is required for amputees to walk with an increased level of biological realism compared to mechanically passive prosthetic systems.
Diverse Antibody Responses to Conserved Structural Motifs in Plasmodium falciparum Circumsporozoite Protein (2019)

Malaria vaccine candidate RTS,S/AS01 is based on the central and C-terminal regions of the circumsporozoite protein (CSP) of P. falciparum. mAb397 was isolated from a volunteer in an RTS,S/AS01 clinical trial, and it protects mice from infection by malaria sporozoites. However, mAb397 originates from the less commonly used VH3-15 germline gene compared to the VH3-30/33 antibodies generally elicited by RTS,S to the central NANP repeat region of CSP. The crystal structure of mAb397 with an NPNA<sub>4</sub> peptide shows that the central NPNA forms a type I β-turn and is the main recognition motif. In most anti-NANP antibodies studied to date, a germline-encoded Trp is used to engage the Pro in NPNA β-turns, but here the Trp interacts with the first Asn. This "conserved" Trp, however, can arise from different germline genes and be located in the heavy or the light chain. Variation in the terminal ψ angles of the NPNA β-turns results in different dispositions of the subsequent NPNA and, hence, different stoichiometries and modes of antibody binding to rsCSP. Diverse protective antibodies against NANP repeats are therefore not limited to a single germline gene response or mode of binding.
Optical frequency domain reflectometry in single-mode fiber (1981)

The backscattered light amplitude is measured from one end of a fiber as a function of optical frequency by tuning a HeNe laser over its linewidth. Fourier transform by a low-frequency electronic spectrum analyzer then reveals the spatial distribution of scattering and of the fiber losses.
Cyclosporine A: A Review of Current Oral and Intravenous Delivery Systems (2007)

As early as 1978, the immunosuppressive effect of cyclosporine A (CsA), a metabolite of the fungus Tolypocladium inflatum (Borel, 1989), was reported to be effective in inhibiting organ rejection in patients receiving kidney transplants from mismatched cadaver donors (Calne et al., 1978) and in the treatment of graft-versus-host disease in patients with acute leukemia following bone marrow transplants (Powles et al., 1978). Today, CsA is still indicated to prevent rejection following solid organ transplantations, prevent and treat graft-vs-host disease following bone marrow transplants, and has also been used in the treatment of autoimmune disease such as psoriasis, rheumatoid arthritis, and nephrotic syndrome (Canadian Pharmacists Association, 2006). The effectiveness of CsA is derived from its ability to specifically and reversibly inhibit immunocompetent lymphocytes in the G(0) and G(1) phase of the cell cycle. The T-helper cells are the main target, but suppression of the T-suppressor cells also occurs. The production and release of lymphokines, including interleukin-2 are also inhibited (Novartis, 2005a). CsA can be administered intravenously as well as orally in the form of a solution or a soft gelatin capsule. The following review will focus on the evolution of the emulsion-based oral formulations from the first generation as Sandimmune to the second generation Neoral, both products of Novartis Pharmaceutical, as well as on the Sandimmune commercial intravenous formulation. The potential of alternative delivery systems, including micelles, micro- and nanoparticles, and liposomes, will also be discussed.
Synthesis of a thymidyl pentamer of deoxyribonucleic guanidine and binding studies with DNA homopolynucleotides. (1995)

Replacement of the phosphodiester linkages of the polyanion DNA with guanidine linkers provides the polycation deoxynucleic guanidine (DNG). The synthesis of pentameric thymidyl DNA is provided. This polycationic DNG species binds with unprecedented affinity and with base-pair specificity to negatively charged poly(dA) to provide both double and triple helices. The dramatic stability of these hybrid structures is shown by their denaturation temperatures (Tm). For example, the double helix of the pentameric thymidyl DNG and poly(dA) does not dissociate in boiling water (ionic strength = 0.12), whereas the Tm for pentameric thymidyl DNA associated with poly(dA) is approximately 13 degrees C (ionic strength = 0.12). The effect of ionic strength on Tm for DNG complexes with DNA shows an opposite correlation compared with double-stranded DNA and is much more dramatic than for double-stranded DNA.
Conformational Cycle of the Archaeosome, a TCP1-like Chaperonin from Sulfolobus shibatae (1995)

The major heat shock proteins in the archaeon Sulfolobus shibatae are similar to the cytosolic eukaryotic chaperonin and form an 18-subunit bitoroidal complex. Two sequence-related subunits constitute a functional complex, named the archaeosome. The archaeosome exists in two distinct conformational states that are part of chaperonin functional cycle. The closed archaeosome complex binds ATP and forms an open complex. Upon ATP hydrolysis, the open complex dissociates into subunits. Free subunits reassemble into a two-ring structure. The equilibrium between the complexes and free subunits is affected by ATP and temperature. Denatured proteins associate with both conformational states as well as with free subunits that form an intermediate complex. These unexpected observations suggest a new mechanism of archaeosome-mediated thermotolerance and protein folding.
Inhibition of CD18-dependent neutrophil adherence reduces organ injury after hemorrhagic shock in primates. (1990)

Neutrophil adherence or aggregation may be important in the development of organ injury after hemorrhagic shock. Monoclonal antibody (MAb) 60.3 prevents both adherence and aggregation. Therefore we investigated MAb 60.3 treatment in prevention of organ injury after hemorrhagic shock in rhesus monkeys (Macaca mulatta). We performed esophagogastroscopy and placed catheters to measure cardiac output, mean arterial pressure, arterial blood gases, and urine output. Blood was removed to decrease CO to 30% of baseline for 90 minutes. Just before resuscitation, MAb 60.3 (2 mg/kg) or saline solution (control) was administered intravenously. Monitoring and fluid resuscitation continued for 24 hours, with lactated Ringer's solution given as a maintenance infusion (4 ml/kg/hr) plus additional lactated Ringer's solution to maintain CO at preshock levels. Esophagogastroscopy was repeated 24 hours after shock. There were two deaths in the control group at about 72 hours and none in the MAb 60.3 group. MAb 60.3-treated animals required less fluid (9.6 +/- 8.8 ml/kg vs 263.8 +/- 225.7 ml/kg), gained less weight (0.08 +/- 0.11 kg vs 0.70 +/- 0.37 kg), and maintained a higher hematocrit level (35.0% +/- 1.0% vs 26.9% +/- 4.9%). All five control animals had gastritis; MAb 60.3-treated animals had none (p less than 0.05; Fisher's exact test). Inhibition of neutrophil adherence or aggregation with MAb 60.3 at the time of resuscitation reduces fluid requirements and gastric injury in monkeys after hemorrhagic shock.