gebhart/patrepeval huggingface dataset:
Bootstrapping (2000)

Bootstrapping analyzes the genesis of personal computing from both technological and social perspectives, through a close study of the pathbreaking work of one researcher, Douglas Engelbart. In his lab at the Stanford Research Institute in the 1960s, Engelbart, along with a small team of researchers, developed some of the cornerstones of personal computing as we know it, including the mouse, the windowed user interface, and hypertext. Today, all these technologies are well known, even taken for granted, but the assumptions and motivations behind their invention are not. Bootstrapping establishes Douglas Engelbart's contribution through a detailed history of both the material and the symbolic constitution of his system's human-computer interface in the context of the computer research community in the United States in the 1960s and 1970s. Engelbart felt that the complexity of many of the world's problems was becoming overwhelming, and the time for solving these problems was becoming shorter and shorter. What was needed, he determined, was a system that would augment human intelligence, co-transforming or co-evolving both humans and the machines they use. He sought a systematic way to think and organize this coevolution in an effort to discover a path on which a radical technological improvement could lead to a radical improvement in how to make people work effectively. What was involved in Engelbart's project was not just the invention of a computerized system that would enable humans, acting together, to manage complexity, but the invention of a new kind of human, "the user." What he ultimately envisioned was a "bootstrapping" process by which those who actually invented the hardware and software of this new system would simultaneously reinvent the human in a new form. The book also offers a careful narrative of the collapse of Engelbart's laboratory at Stanford Research Institute, and the further translation of Engelbart's vision. It shows that Engelbart's ultimate goal of coevolution came to be translated in terms of technological progress and human adaptation to supposedly user-friendly technologies. At a time of the massive diffusion of the World Wide Web, Bootstrapping recalls the early experiments and original ideals that led to today's "information revolution."
Is Demodex really non-pathogenic? (2000)

Although usually considered a non-pathogenic parasite in parasitological textbooks, Demodex folliculorum has been implicated as a causative agent for some dermatological conditions, such as rosacea-like eruptions and some types of blepharitis. Several anecdotal reports have demonstrated unequivocal tissue damage directly related to the presence of the parasite. However, this seems to be exceedingly rare, in contrast with the marked prevalence of this infestation. We have had the opportunity to observe one of such cases. A 38-year-old woman presented with rosacea-like papular lesions in her right cheek. Histopathological examination revealed granulomatous dermal inflammation with a well-preserved mite phagocytized by a multinucleated giant cell. This finding may be taken as an evidence for the pathogenicity of the parasite, inasmuch as it does not explain how such a common parasite is able to produce such a rare disease.
Coagulation Factor IX Residues G4−Q11 Mediate Its Interaction with a Shared Factor IX/IXa Binding Site on Activated Platelets but Not the Assembly of the Functional Factor X Activating Complex (1998)

High-affinity, specific factor IX/IXa binding to platelets is mediated at least in part by amino acids (G4-Q11) exposed on the surface of the gamma-carboxyglutamic acid (Gla) domain. Rationally designed, conformationally constrained synthetic peptides were screened for their capacity to inhibit factor IXa binding to platelets. Each of these peptides (G4-Q11, S3-L6, and F9-Q11) acted alone to inhibit factor IXa binding to approximately 50% of the 500-600 sites/platelet with Ki values of 2.9 nM (G4-Q11), 24 nM (S3-L6), and 240 nM (F9-Q11), compared with native factor IXa (Ki approximately 2.5 nM). The two peptides S3-L6 and F9-Q11 added together at equimolar concentration demonstrated approximately 50-fold synergism (Ki = 2.4 nM). Although both factor IX and the Gla peptide (G4-Q11) displaced 100% of bound factor IX and approximately 50% of bound factor IXa, factor IX was ineffective (at > 1000-fold molar excess) and the Gla domain peptide (G4-Q11) was relatively ineffective (Ki = 165 microM) in inhibiting platelet receptor-mediated factor X activation by factor IXa. We conclude that the Gla domain (G4-Q11) of factor IXa contains two conformationally constrained loop structures that mediate binding of factor IX/IXa to a shared site on activated human platelets which is separate and distinct from the site used by the enzyme, factor IXa, for assembly of the factor X activating complex.
The American Put Option Valued Analytically (1984)

ABSTRACT An analytic solution to the American put problem is derived herein. The hedge ratio and other derivatives of the solution are presented. The formula derived implies an exact duplicating portfolio for the American put consisting of discount bonds and stock sold short. The formula is extended to consider put options on stocks paying cash dividends. A polynomial expression is developed for evaluating these formulae. Values and hedge ratios for puts on both dividend and nondividend paying stocks are calculated, tabulated, and compared with values derived by numerical integration and binomial approximation. As with European options, evaluating an analytic formula is more efficient than approximating the stock price process or the partial differential equation by binomial or finite difference methods. Finally, applications of this American put solution are discussed.
Organization of the transcriptional unit of a human class II histocompatibility antigen: HLA-DR heavy chain (1983)

A total of 5724 base pairs of a recombinant phage DNA containing a human HLA-DR heavy chain gene including flanking regions has been analyzed. The regions corresponding to all the exons have been identified. The sites of initiation of transcription and polyadenylation have been determined. A large intron of 2399 base pairs separates the first exon containing the 5' untranslated region and the signal peptide from the second exon containing the N-terminal peptide domain.
Effects of Calcium Codoping on Charge Traps in LSO:Ce Crystals (2009)

Experimental studies of Lu <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sub> SiO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">5</sub> :Ce (LSO:Ce) crystals codoped with various concentrations of Ca (0, 0.1, 0.2, 0.3, and 0.4 at% in the melt) are presented. The scintillation and optical properties including photoluminescence decay, emission, excitation, absorption, afterglow and thermoluminescence properties are investigated as a function of Ca concentration. Experimental data show Ca codoping significantly reduces the trapped charge population in the crystal matrix. Hence, the scintillation decay time of LSO:Ce is shortened and the afterglow is suppressed. Thermoluminescence studies show a strong correlation between the integrated thermoluminescence intensity and the Ca concentration.
p38 Mitogen-Activated Protein Kinase Is Activated and Linked to TNF-α Signaling in Inflammatory Bowel Disease (2002)

Inflammatory bowel diseases (IBD)--Crohn's disease and ulcerative colitis--are relapsing chronic inflammatory disorders which involve genetic, immunological, and environmental factors. The regulation of TNF-alpha, a key mediator in the inflammatory process in IBD, is interconnected with mitogen-activated protein kinase pathways. The aim of this study was to characterize the activity and expression of the four p38 subtypes (p38alpha-delta), c-Jun N-terminal kinases (JNKs), and the extracellular signal-regulated kinases (ERK)1/2 in the inflamed intestinal mucosa. Western blot analysis revealed that p38alpha, JNKs, and ERK1/2 were significantly activated in IBD, with p38alpha showing the most pronounced increase in kinase activity. Protein expression of p38 and JNK was only moderately altered in IBD patients compared with normal controls, whereas ERK1/2 protein was significantly down-regulated. Immunohistochemical analysis of inflamed mucosal biopsies localized the main expression of p38alpha to lamina propria macrophages and neutrophils. ELISA screening of the supernatants of Crohn's disease mucosal biopsy cultures showed that incubation with the p38 inhibitor SB 203580 significantly reduced secretion of TNF-alpha. In vivo inhibition of TNF-alpha by a single infusion of anti-TNF-alpha Ab (infliximab) resulted in a highly significant transient increase of p38alpha activity during the first 48 h after infusion. A significant infliximab-dependent p38alpha activation was also observed in THP-1 myelomonocytic cells. In human monocytes, infliximab enhanced TNF-alpha gene expression, which could be inhibited by SB 203580. In conclusion, p38alpha signaling is involved in the pathophysiology of IBD.
Food-initiated outbreak of methicillin-resistant Staphylococcus aureus analyzed by pheno- and genotyping (1995)

An outbreak of methicillin-resistant Staphylococcus aureus (MRSA) involving 27 patients and 14 health-care workers (HCW) was studied. The outbreak started in the hematology unit of the University Hospital Rotterdam, Dijkzigt, The Netherlands, and spread to the surgical unit. Twenty-one patients (77.8%) developed clinical disease, and five died. Subsequently, MRSA was detected in food and in the throat of one of the HCW who prepared food for hematology patients. Food contaminated by an HCW most likely caused the first case of MRSA septicemia. This route of transmission has not been described before. The outbreak strain was probably transmitted to the surgical unit by a colonized nurse, where it caused an explosive outbreak. Airborne probably transmitted to the surgical unit by a colonized nurse, where it caused an explosive outbreak. Airborne MRSA transmission played an important role in disseminating the organism. The outbreak was controlled within 6 months by intensifying surveillance, temporarily closing the affected wards, treating carriers, and instituting an MRSA ward outside the hospital. Phage typing, insertion sequence probing, protein A gene typing, and DNA fingerprinting by PCR revealed that all outbreak-related isolates were identical. By pulsed-field gel electrophoresis, all but one of the outbreak-related isolates were determined to be identical. Protein A gene typing identified numerous (11) repeat units in all outbreak-related isolates, which supports the suggestion that the outbreak strain may have been more virulent and more transmissible than other MRSA strains. Pheno- and genotyping studies underlined the value of DNA fingerprinting methods for investigation of MRSA epidemiology. Optimal discriminatory power was achieved by combining the results of four genotyping methods.
“Total Synthesis” Supramolecular Style: Design and Hydrogen-Bond-Directed Assembly of Ternary Supermolecules (2001)

Getting the right balance between intermolecular interactions is crucial for the synthesis of supermolecules in a preconceived manner. The three-component supermolecule in the ternary cocrystal of 3,5-dinitrobenzoic acid, isonicotinamide, and 4-(dimethylamino)benzoic acid (1:1:1) assembles through a "primary" (between the stronger acid and pyridine) and a "secondary" hydrogen-bonding interaction (between the weaker acid and amide).
Approaches to allele frequency determination (2000)

Hundreds of thousands of candidate single nucleotide polymorphisms (SNPs) are being identified as part of the human genome project. For these markers to be useful in any study their allele frequencies in the study population must be known, or much effort will be wasted when markers with the wrong characteristics are selected for studies involving large-scale genotyping of SNP markers. Because allele frequency estimations by genotyping a representative sample of a population is a costly endeavour, an obvious strategy to reduce the cost is to identify accurate and efficient approaches to allele frequency estimation using DNA pools. There are several allele frequency estimation approaches currently in use, including PCR-RFLP analysis, DNA sequencing, the Taqman assay and kinetic PCR. All these approaches give reasonably good allele frequency estimates. Accurate and efficient allele frequency estimation in DNA pools will reduce the cost and effort needed in genetic and association studies and opens up ways to perform pharmacogenomic and evolutionary studies efficiently.
<title>Hierarchical brain mapping via a generalized Dirichlet solution for mapping brain manifolds</title> (1995)

In this paper we present a coarse-to-fine approach for the transformation of digital anatomical textbooks from the ideal to the individual that unifies the work on landmark deformations and volume based transformation. The Hierarchical approach is linked to the Biological problem itself, coming out of the various kinds of information which is provided by the anatomists. This information is in the form of points, lines, surfaces and sub-volumes corresponding to 0, 1, 2, and 3 dimensional sub-manifolds respectively. The algorithm is driven by these sub- manifolds. We follow the approach that the highest dimensional transformation is a result from the solution of a sequence of lower dimensional problems driven by successive refinements or partitions of the images into various Biologically meaningful sub-structures.
Update on clinical role of tamoxifen (2003)

Recent data showing a survival advantage for the aromatase inhibitor letrozole compared with tamoxifen in the advanced setting and improvement in disease-free survival for the aromatase inhibitor anastrozole versus tamoxifen as adjuvant treatment may herald a major shift in standard first-line endocrine therapies for both advanced and early disease and ultimately chemoprevention of breast cancer. Other agents including newer SERMs and pure antiestrogens are undergoing phase III clinical trials and future endocrine and biological therapies are likely to include more selective and targeted therapies, which may be efficacious in both hormone-sensitive and receptor-negative disease.
G-Quadruplexes Form Ultrastable Parallel Structures in Deep Eutectic Solvent (2013)

G-quadruplex DNA is highly polymorphic. Its conformation transition is involved in a series of important life events. These controllable diverse structures also make G-quadruplex DNA a promising candidate as catalyst, biosensor, and DNA-based architecture. So far, G-quadruplex DNA-based applications are restricted done in aqueous media. Since many chemical reactions and devices are required to be performed under strictly anhydrous conditions, even at high temperature, it is challenging and meaningful to conduct G-quadruplex DNA in water-free medium. In this report, we systemically studied 10 representative G-quadruplexes in anhydrous room-temperature deep eutectic solvents (DESs). The results indicate that intramolecular, intermolecular, and even higher-order G-quadruplex structures can be formed in DES. Intriguingly, in DES, parallel structure becomes the G-quadruplex DNA preferred conformation. More importantly, compared to aqueous media, G-quadruplex has ultrastability in DES and, surprisingly, some G-quadruplex DNA can survive even beyond 110 °C. Our work would shed light on the applications of G-quadruplex DNA to chemical reactions and DNA-based devices performed in an anhydrous environment, even at high temperature.
A Technique for Collision Block of Peripheral Nerve: Frequency Dependence (1981)

A previously reported stimulation technique which elicits a unidirectionally propagated nerve action potential has been evaluated with repetition rates from 10 to 100 Hiz. Block of propagation in one direction from the stimulus site was sustained up to 50 Hz with monophasic stimulation and 30 Hz with biphasic stimulation. The use of long stimulating pulses produces pronounced degradation of the block at high frequencies.
Fast decipherment algorithm for RSA public-key cryptosystem (1982)

A fast algorithm is presented for deciphering cryptograms involved in the public-key cryptosystem proposed by Rivest, Shamir and Adleman. The deciphering method is based on the Chinese remainder theorem and on improved modular multiplication algorithms.
A Radioimmunoassay Using a Monoclonal Antibody to Monitor the Course of Epithelial Ovarian Cancer (1983)

The murine monoclonal antibody OC 125 reacts with an antigen (CA 125) common to most nonmucinous epithelial ovarian carcinomas. An assay has been developed to detect CA 125 in serum. By this assay, only 1 per cent of 888 apparently healthy persons and 6 per cent of 143 patients with nonmalignant disease had serum CA 125 levels above 35 U per milliliter. In contrast, 83 of 101 patients (82 per cent) with surgically demonstrated ovarian carcinoma had elevated levels of antigen. In 38 patients with epithelial ovarian carcinoma monitored on 2 to 18 occasions during 2 to 60 months, antigen levels ranged from less than 1 to more than 8000 U per milliliter. Rising or falling levels of CA 125 correlated with progression or regression of disease in 42 of 45 instances (93 per cent). Determination of CA 125 levels may aid in monitoring the response to treatment in patients with epithelial ovarian cancer.
In vivo inhibition of superoxide dismutase in mice by diethyldithiocarbamate. (1976)

Superoxide dismutase was assayed by a method which takes advantage of the inhibitory action of superoxide dismutase (or tissues which contain superoxide dismutase) on the rate of autooxidation of 6-hydroxydopamine. Incubation of pure superoxide dismutase of homogenates of brain or liver with 10(-3) M diethyldithiocarbamate for 1.5 hours resulted in total loss of superoxide dismutase activity. Inhibition of superoxide dismutase was not reversed by dialysis, but after dialysis, enzymatic activity was restored with CuSO4. When 1.5 g of diethyldithiocarbamate/kg were injected into mice, the superoxide dismutase activity at 3 hours was decreased by 86%, 71%, and 48%, respectively, in whole blood, liver, and brain. A dose of 0.5 g of diethyldithiocarbamate/kg lowered the superoxide dismutase activity by 42% in liver at 3 hours. A study of the time course for inhibiton of superoxide dismutase in liver after 1.5 g of diethyldithiocarbamate/kg, showed a maximum decrease (81%) within 1 hour, with a slow return to 64% of normal by 24 hours. Inhibition of superoxide dismutase in vivo and in vitro was confirmed with other assay systems based on the autooxidation of pyrogallol or epinephrine or on reduction of cytochrome c or intro blue tetrazolium. Treatment of animals with diethyldithiocarbamate may provide a useful experimental model to study the role of superoxide dismutase in various tissues.
An FIR cascade structure for adaptive linear prediction (1998)

An alternative structure for adaptive linear prediction is proposed in which the adaptive filter is replaced by a cascade of independently adapting, low-order stages, and the prediction is generated by means of successive refinements. When the adaptation algorithm for the stages is LMS, the associated short filters are less affected by eigenvalue spread and mode coupling problems and display a faster convergence to their steady-state value. Experimental results show that a cascade of second-order LMS filters is capable of successfully modeling most input signals, with a much smaller MSE than LMS or lattice LMS predictors in the early phase of the adaptation. Other adaptation algorithms can be used for the single stages, whereas the overall computational cost remains linear in the number of stages, and very fast tracking is achieved.
Determination of adenosine deaminase binding domain on CD26 and its immunoregulatory effect on T cell activation (1997)

CD26, a 110-kDa cell surface glycoprotein, exhibits dipeptidyl peptidase IV enzyme activity and plays an important role in T cell costimulation. In the present study, we examined both the exact adenosine deaminase (ADA) binding domain on CD26 and the functional consequences of mutated CD26 transfectants that were deficient for cell surface ADA. Using CD26 deletion, human-rat swap, and point mutations, we found that the residues of L340, V341, A342, and R343 on the CD26 molecule were essential amino acids for ADA binding. When these amino acids were mutated and transfected into Jurkat cells, the resultant CD26 transfectants expressed only CD26, not ADA, on the cell surface. The amount of IL-2 produced by wild-type and mutated CD26 transfectants was almost the same following stimulation with anti-CD3 plus PMA. However, the mutated CD26 transfectants were much more sensitive to the inhibitory effect of adenosine on IL-2 production than were the wild CD26 transfectants. These data suggest that ADA on the cell surface does not directly involve T cell activation. Conversely, CD26 alone does not result in modulating the inhibitory effect of adenosine. Only the ADA bound to CD26 on the cell surface was functional and could counteract the inhibitory effect of elevated extracellular adenosine.
First-in-human Mutation-targeted siRNA Phase Ib Trial of an Inherited Skin Disorder (2009)

The rare skin disorder pachyonychia congenita (PC) is an autosomal dominant syndrome that includes a disabling plantar keratoderma for which no satisfactory treatment is currently available. We have completed a phase Ib clinical trial for treatment of PC utilizing the first short-interfering RNA (siRNA)-based therapeutic for skin. This siRNA, called TD101, specifically and potently targets the keratin 6a (K6a) N171K mutant mRNA without affecting wild-type K6a mRNA. The safety and efficacy of TD101 was tested in a single-patient 17-week, prospective, double-blind, split-body, vehicle-controlled, dose-escalation trial. Randomly assigned solutions of TD101 or vehicle control were injected in symmetric plantar calluses on opposite feet. No adverse events occurred during the trial or in the 3-month washout period. Subjective patient assessment and physician clinical efficacy measures revealed regression of callus on the siRNA-treated, but not on the vehicle-treated foot. This trial represents the first time that siRNA has been used in a clinical setting to target a mutant gene or a genetic disorder, and the first use of siRNA in human skin. The callus regression seen on the patient's siRNA-treated foot appears sufficiently promising to warrant additional studies of siRNA in this and other dominant-negative skin diseases.
New paradigms in inflammatory signaling in vascular endothelial cells (2013)

Inflammation is a basic cellular process in innate and adaptive immunity. Vascular endothelial cells play an important role in the initiation, amplification, and resolution of the inflammatory response. Deregulated inflammatory response is implicated in a variety of cardiovascular diseases such as atherosclerosis, obesity, diabetes, and hypertension. Recent studies have made significant progresses in the understanding of the complex molecular pathways that mediate the pro- and anti-inflammatory signaling in endothelial cells (ECs). Specifically, a number of macromolecular complexes termed as signalosomes have been identified to integrate the proinflammatory signaling from the membrane receptors to key transcription factors such as nuclear factor-κB (NF-κB). Inflammasomes are associated with the pattern-recognition receptors such as Toll-like receptors (TLRs), nucleotide-binding oligomerization-domain (NOD)-like receptors (NLRs) to mediate innate immunity responses. Emerging evidence has also revealed that noncoding microRNAs constitute a new class of intra- and intercellular signaling molecules to modulate inflammation in ECs. Thus this article will briefly summarize these new mechanisms with a special emphasis in the context of cardiovascular diseases.