gebhart/patrepeval huggingface dataset:
Average-case complexity of the Whitehead problem for a free group (2021)

The worst-case complexity of group-theoretic algorithms has been studied for a long time. Generic-case complexity, or complexity on random inputs, was introduced and studied relatively recently. In this paper, we address the average-case complexity (i.e., the expected runtime) of algorithms that solve a well-known problem, the Whitehead problem in a free group, which is: given two elements of a free group, find out whether there is an automorphism that takes one element to the other. First we address a special case of the Whitehead problem, namely deciding if a given element of a free group is part of a free basis. We show that there is an algorithm that, on a cyclically reduced input word, solves this problem and has constant (with respect to the length of the input) average-case complexity. For the general Whitehead problem, we show that the classical Whitehead algorithm has linear average-case complexity if the rank of the free group is 2. We argue that the same should be true in a free group of any rank but point out obstacles to establishing this general result.
Decline in Slow Vital Capacity Predicts Respiratory Insufficiency, Use of Assisted Ventilation, Tracheostomy or Death in ALS (P3.186) (2016)

Objective: to determine the relationship between pulmonary measures commonly used in ALS. Background: Tirasemtiv, a selective skeletal muscle activator, significantly reduced the decline in slow vital capacity (SVC) over 12 weeks in the Phase 2b clinical trial, BENEFIT-ALS. To understand this finding, we investigated the natural history of SVC and its relationship to other measures of respiratory function in placebo patients from the dexpramipexole Phase 3 clinical trial, EMPOWER. Methods: 469 patients randomized to placebo in EMPOWER were included; follow-up was 1.5 years. Slope of decline in SVC was calculated overall and in different subgroups. Cox regression modelled the time to clinical events from Month 6 visit to the end of follow-up using the slope of SVC change from baseline to the Month 6 visit as an explanatory variable. Pearson Product Moment correlation coefficient (r) assessed associations between SVC and other variables. Results: Slope of SVC was -0.090[percnt]/day (95[percnt]CIs: -0.098, -0.082). Older subjects, subjects with initial ALSFRS-R less than 39, and bulbar onset subjects all had a steeper slope of decline (-0.12[percnt]/day, -0.10[percnt]/day, and -0.10[percnt]/day respectively). Patients with SVC decline by 0.05[percnt]/day from baseline to the Month 6 visit had a reduced risk for the earlier of death or any decline in the respiratory subdomain of ALSFRS-R (19[percnt]); or onset of respiratory insufficiency (22[percnt]); or tracheostomy (23[percnt]); and for the risk of death (23[percnt]) after the Month 6 visit (all p<0.0001). The correlation of change from baseline in SVC and the respiratory subdomain of the ALSFRS-R (r = 0.26) was weak (p<0.0001). Conclusion: Decline of SVC predicted the risk of meaningful clinical events, including the decline in the respiration subdomain of ALSFRS-R, respiratory insufficiency, tracheostomy or death. The weak correlation of change in SVC with the ALSFRS-R respiratory questions suggests that they may not be sensitive indicators of respiratory dysfunction.
Facile Synthesis of a Fluorescent Deoxycytidine Analogue Suitable for Probing the RecA Nucleoprotein Filament (2001)

We report the synthesis of the fluorescent 2'-deoxycytidine analogue 5-methylpyrimidin-2-one nucleoside, its incorporation at three specified sites in a single 60-nucleotide DNA molecule, and the use of its total and polarized intrinsic fluorescence to characterize RecA-DNA complexes. [reaction: see text]
Linear Sparse Array Synthesis With Minimum Number of Sensors (2010)

The number of sensors employed in an array affects the array performance, computational load, and cost. Consequently, the minimization of the number of sensors is of great importance in practice. However, relatively fewer research works have been reported on the later. In this paper, a novel optimization method is proposed to address this issue. In the proposed method, the improved genetic algorithm that has been presented at a conference recently, is used to optimize the weight coefficients and sensor positions of the array. Sensors that contribute the least to the array performance are then removed systematically until the smallest acceptable number of sensors is obtained. Specifically, this paper reports the study on the relationship between the peak sidelobe level and the sensor weights, and uses the later to select the sensors to be removed. Through this approach, the desired beam pattern can be synthesized using the smallest number of sensors efficiently. Numerical results show that the proposed sensor removal method is able to achieve good sidelobe suppression with a smaller number of sensors compared to other existing algorithms. The computational load required by our proposed approach is about one order less than that required by other existing algorithms too.
Autophosphorylation-based Calcium (Ca2+) Sensitivity Priming and Ca2+/Calmodulin Inhibition of Arabidopsis thaliana Ca2+-dependent Protein Kinase 28 (CPK28) (2017)

Plant calcium (Ca<sup>2+</sup>)-dependent protein kinases (CPKs) represent the primary Ca<sup>2+</sup>-dependent protein kinase activities in plant systems. CPKs are composed of a dual specificity (Ser/Thr and Tyr) kinase domain tethered to a calmodulin-like domain (CLD) via an autoinhibitory junction (J). Although regulation of CPKs by Ca<sup>2+</sup> has been extensively studied, the contribution of autophosphorylation in controlling CPK activity is less well understood. Furthermore, whether calmodulin (CaM) contributes to CPK regulation, as is the case for Ca<sup>2+</sup>/CaM-dependent protein kinases outside the plant lineage, remains an open question. We therefore screened a subset of plant CPKs for CaM binding and found that CPK28 is a high affinity Ca<sup>2+</sup>/CaM-binding protein. Using synthetic peptides and native gel electrophoresis, we coarsely mapped the CaM-binding domain to a site within the CPK28 J domain that overlaps with the known site of intramolecular interaction between the J domain and the CLD. Peptide kinase activity of fully dephosphorylated CPK28 was Ca<sup>2+</sup>-responsive and was inhibited by Ca<sup>2+</sup>/CaM. Using <i>in situ</i> autophosphorylated protein, we expand on the known set of CPK28 autophosphorylation sites, and we demonstrate that, unexpectedly, autophosphorylated CPK28 had enhanced kinase activity at physiological concentrations of Ca<sup>2+</sup> compared with the dephosphorylated protein, suggesting that autophosphorylation functions to prime CPK28 for Ca<sup>2+</sup> activation and might also allow CPK28 to remain active when Ca<sup>2+</sup> levels are low. Furthermore, CPK28 autophosphorylation substantially reduced sensitivity of the kinase to Ca<sup>2+</sup>/CaM inhibition. Overall, our analyses uncover new complexities in the control of CPK28 and provide mechanistic support for Ca<sup>2+</sup> signaling specificity through Ca<sup>2+</sup> sensor priming.
Leptomycin B Inhibits Equine Infectious Anemia Virus Rev and Feline Immunodeficiency Virus Rev Function but Not the Function of the Hepatitis B Virus Posttranscriptional Regulatory Element (1998)

Human immunodeficiency virus type 1 Rev export depends upon the presence of the nuclear export signal (NES), a leucine-rich stretch of hydrophobic amino acids. Recently, the nuclear NES-binding receptor has been identified as CRM1 or exportin 1. Rev export has been shown to be CRM1 dependent. The function of the atypical NES-containing Rev-like proteins of equine infectious anemia virus (EIAV) and feline immunodeficiency virus (FIV) is inhibited by leptomycin B, a drug that specifically blocks NES-CRM1 interactions. These data suggest that the function of atypical NES-containing proteins is CRM1 dependent. In contrast to the inhibition of EIAV Rev and FIV Rev, the cytoplasmic accumulation of hepatitis B virus (HBV) posttranscriptional regulatory element (PRE)-containing and Mason-Pfizer monkey virus (MPMV) constitutive transport element (CTE)-containing RNAs is not inhibited by leptomycin B treatment. We conclude that the HBV PRE, like the MPMV CTE, functions independently of an NES receptor-exportin 1 interaction.
Time-Dependent Proinflammatory Responses Shape Virus Interference during Coinfections of Influenza A Virus and Influenza D Virus (2022)

Both influenza A virus (IAV) and influenza D virus (IDV) are enzootic in pigs. IAV causes approximately 100% morbidity with low mortality, whereas IDV leads to only mild respiratory diseases in pigs. In this study, we performed a series of coinfection experiments in vitro and in vivo to understand how IAV and IDV interact and cause pathogenesis during coinfection. The results showed that IAV inhibited IDV replication when infecting swine tracheal epithelial cells (STECs) with IAV 24 or 48 h prior to IDV inoculation and that IDV suppressed IAV replication when IDV preceded IAV inoculation by 48 h. Virus interference was not identified during simultaneous IAV/IDV infections or with 6 h between the two viral infections, regardless of their order. The interference pattern at 24 and 48 h correlated with proinflammatory responses induced by the first infection, which, for IDV, was slower than for IAV by about 24 h. The viruses did not interfere with each other if both infected the cells before proinflammatory responses were induced. Coinfection in pigs further demonstrated that IAV interfered with both viral shedding and virus replication of IDV, especially in the upper respiratory tract. Clinically, coinfection of IDV and IAV did not show significant enhancement of disease pathogenesis, compared with the pigs infected with IAV alone. In summary, this study suggests that interference during coinfection of IAV and IDV is primarily due to the proinflammatory response; therefore, it is dependent on the time between infections and the order of infection. This study facilitates our understanding of virus epidemiology and pathogenesis associated with IAV and IDV coinfection.
Process-Driven Input Profiling for Plastics Processing (2007)

Most plastic processing set points are variables that need to be defined for each sample point of the cycle. However, in the absence of on-line measures of part quality, the set points cannot be defined by feedback and need to be prescribed a priori for the entire cycle. In conventional practice, the shape of each set-point profile is defined either heuristically, according to qualitative experience, or mechanistically, to enforce a predefined trajectory for a simulated internal process state that is used as a surrogate measure of part quality (e.g., the velocity profile defined to dictate a constant melt front velocity). The purpose of this study is twofold: (i) to evaluate the efficacy of using a single internal state as the surrogate of part quality, and (ii) to explore the feasibility of devising a multivariate profiling approach, where indices of multiple process states act as surrogates of part quality. For this study, an injection-compression molding process used for production of digital video disks was considered as the development domain, and a pseudo-optimal cycle of the process was found by reinforcement learning to provide a basis for evaluating the ideal behavior of the process states. Compared to conventional molding, the results indicate that the asymmetric process capability index, CPK, was increased by ∼50% with velocity profile optimization and to 120% with both velocity profile and pressure profile optimization. Two general conclusions result. First, velocity and pressure profiling provide important degrees of freedom for optimizing process control and maximizing part quality. Second, estimators for unobservable process states, in this case birefringence and warpage, can be used to develop different machine profiles to selectively trade off multiple quality attributes according to user preferences.
"Targeted Therapy with Monoclonal Antibodies: The New Generation of Pharmaceuticals" (2006)

The last decade has witnessed a revolution in pharmaceutical sciences and commercial products with the introduction and intensification of biological products. Foremost has been the development and commercialization of antibodies, particularly for the therapy of cancer, with 8 such products already approved in the USA and hundreds of product candidates in various stages of clinical development. Although monoclonal antibodies have been pursued as new commercial candidates for about 30 years, advances in antibody engineering were required to de-immunize them for repeated human use, and when used as targeting agents, various constructs with isotopes, drug, and toxins have been developed and commercialized. As new targets become identified, the diverse antibody products are gaining in attention as prospective new therapeutics even beyond cancer, such as in the therapy of autoimmune, infectious, and neurodegenerative diseases. Not only are new antibody constructs of multifunctional nature being developed for enhanced potency, but new delivery systems involving methods of separating the targeting moiety from the effector molecules (radionuclided, drugs, toxins, cytokines), such as in so-called pretargeting methods, are under development. These advances have resulted in the concept of targeted disease therapy, attended by a better safety profile for this new class of pharmaceuticals, and are being used increasingly in combination with conventional cytotoxic drugs approved for the therapy of cancer and immune diseases. These disease-targeting antibodies, however, should soon decrease the dependence on traditional cytotoxic drugs by targeting such agents more selectively as immunoconjugates, especially with pretargeting technologies.
Guest-responsive structural changes of porphyrinogen inclusion crystals: a long-range cooperative effect on guest inclusion (1997)

meso-Octaethylporphyrinogen inclusion crystals with lower alcohols undergo reversible guest-responsive structural changes, for which a long-range cooperative effect with a Hill coefficient of 40 is observed.
NB‐UVB phototherapy response of different body regions in non‐segmental vitiligo (2023)

NB-UVB phototherapy response of different body regions in non-segmental vitiligoDear Editor, Narrow-band ultraviolet B (NB-UVB) is a widely used treatment for non-segmental vitiligo (NSV).It is frequently combined with topical therapy (such as calcineurin inhibitors and/or corticosteroids), due to the superiority of combination therapy above monotherapy. [1][2]2][3][4] In cases of rapidly spreading vitiligo, systemic steroids in an oral minipulse (OMP) scheme are often added to this therapy to arrest
Design and characterization of bi-functionalized scaffolds for blood vessels tissues (2013)

Coronary artery and peripheral vascular diseases are a leading cause of death and disability worldwide. Vascular bypass can be performed with autologous or synthetic grafts. Although both approaches can be used in the treatment of large diameter vessels, less than 50% of small diameter grafts remain patent 5 years after implantation. A possible solution could be offered by vascular tissue engineering. Blood vessels are composed of three concentric layers: the tunica intima, composed of endothelial cells, that inhibits platelet activation and prevents thrombus formation; the tunica media, composed of concentrically organized smooth muscle cells and separated from the tunica intima by an internal elastic lamina; the tunica adventitia, made of fibroblast cells surrounded by extracellular matrix with a high content of collagen. The aim of this work was the production of a small diameter tubular scaffolds, based on a blend of gelatin, gellan and elastin, in order to mimic the chemical composition of native vessels. A double functionalization with signalling peptides was then performed on the scaffolds, with the aim to promote the regeneration of blood vessels with the same cell organization of the native ones.
HIV Infection in 1968-Reply (1989)

In Reply. — The purpose of our Brief Report was to document human immunodeficiency type 1 (HIV-1) infection in 1968 and 1969 in the United States in a patient who, as we suggested earlier in 1984, 1 fulfilled the Centers for Disease Control diagnostic criteria for AIDS. We established HIV-1 infection by two specific, highly sensitive independent tests (Western blot and antigen capture immunoassays) and also attempted to eliminate artifacts due to storage through use of appropriate controls. Although it was not our purpose to review suspected AIDS cases in the pre-AIDS era, we did cite one review of the early literature back to 1902, 2 which antedated and overlapped the report of Huminer et al; the latter was not yet available to us at the time of submission of our article for publication. It is noteworthy that the referenced cases with positive serological tests for human immunodeficiency virus
Comprehensive population-based genome sequencing provides insight into hematopoietic regulatory mechanisms (2016)

Genetic variants affecting hematopoiesis can influence commonly measured blood cell traits. To identify factors that affect hematopoiesis, we performed association studies for blood cell traits in the population-based Estonian Biobank using high-coverage whole-genome sequencing (WGS) in 2,284 samples and SNP genotyping in an additional 14,904 samples. Using up to 7,134 samples with available phenotype data, our analyses identified 17 associations across 14 blood cell traits. Integration of WGS-based fine-mapping and complementary epigenomic datasets provided evidence for causal mechanisms at several loci, including at a previously undiscovered basophil count-associated locus near the master hematopoietic transcription factor CEBPA The fine-mapped variant at this basophil count association near CEBPA overlapped an enhancer active in common myeloid progenitors and influenced its activity. In situ perturbation of this enhancer by CRISPR/Cas9 mutagenesis in hematopoietic stem and progenitor cells demonstrated that it is necessary for and specifically regulates CEBPA expression during basophil differentiation. We additionally identified basophil count-associated variation at another more pleiotropic myeloid enhancer near GATA2, highlighting regulatory mechanisms for ordered expression of master hematopoietic regulators during lineage specification. Our study illustrates how population-based genetic studies can provide key insights into poorly understood cell differentiation processes of considerable physiologic relevance.
Low‐Temperature Reductive Aminolysis of Carbohydrates to Diamines and Aminoalcohols by Heterogeneous Catalysis (2017)

Short amines, such as ethanolamines and ethylenediamines, are important compounds in today's bulk and fine chemicals industry. Unfortunately, current industrial manufacture of these chemicals relies on fossil resources and requires rigorous safety measures when handling explosive or toxic intermediates. Inspired by the elegant working mechanism of aldolase enzymes, a novel heterogeneously catalyzed process-reductive aminolysis-was developed for the efficient production of short amines from carbohydrates at low temperature. High-value bio-based amines containing a bio-derived C2 carbon backbone were synthesized in one step with yields up to 87 C%, in the absence of a solvent and at a temperature below 405 K. A wide variety of available primary and secondary alkyl- and alkanolamines can be reacted with the carbohydrate to form the corresponding C2-diamine. The presented reductive aminolysis is therefore a promising strategy for sustainable synthesis of short, acyclic, bio-based amines.
Management of Malignant Esophageal Stricture with Esophageal Dilation and Esophageal Stents (1994)

Esophageal dilatation and endoprosthesis insertion are very useful techniques in the palliation of malignant esophageal strictures. Patients with tracheoesophageal fistula or tumors poorly responsive to dilation or other therapies will achieve benefit from esophageal stent placement. Although further studies are needed, it appears that the use of expansile metallic stents may be advantageous compared with the standard plastic stents.
Transmission electron microscopy study on the crystallization and boron distribution of CoFeB/MgO/CoFeB magnetic tunnel junctions with various capping layers (2009)

High-resolution transmission electron microscopy and electron energy-loss spectroscopy (EELS) were used to study the microstructural properties of CoFeB/MgO/CoFeB magnetic tunnel junctions (MTJs) with various capping layers. Crystallization of CoFeB layers was strongly dependent on the capping materials, and was affected by B diffusion. With NiFe-cap MTJs, CoFeB crystallized from the cap interface and formed a fcc structure; on the other hand, with Ta- and Ti-cap MTJs, CoFeB crystallized from the MgO interface and formed a bcc structure. EELS analysis showed that B mainly diffused to the capping layers and rarely to the MgO layers with increasing temperature. With Ti-cap MTJs, B diffusion caused hcp-Ti crystals to form an amorphous structure and CoFeB crystallized at lower temperature.
Protein‐Structure‐Based Prediction of Animal Model Suitability for Pharmacodynamic Studies of Subtype‐Selective Estrogens (2006)

Subtype-selective estrogens are of increasing importance as tools used to unravel physiological roles of the estrogen receptors, ERalpha and ERbeta, in various species. Although human ERalpha and ERbeta differ by only two amino acids within the binding pockets, we and others recently succeeded in generating subtype-selective agonists. We have proposed that the selectivity of the steroidal compounds 16alpha-lactone-estradiol (16alpha-LE(2), hERalpha selective) and 8beta-vinyl-estradiol (8beta-VE(2), hERbeta selective) is based on the interaction of certain substituents of these compounds with essentially one amino acid in the respective ER binding pockets. For in vitro and ex vivo pharmacological experiments with these compounds we intended to use bovine tissues available from slaughterhouses in larger quantities. Using homology modeling techniques we determined that the amino acid conferring high hERbeta-selectivity to 8beta-VE(2) is not exchanged between human and bovine ERalpha and bovine ERbeta. Thus, we predicted our steroidal hERbeta-selective compound to exhibit only weak agonistic activity at bERbeta and that bovine tissue is therefore not suited for investigation of ERbeta functions. The situation is presumably identical for pig, sheep, and the common marmoset, whereas rats, mice, and rhesus macaques are appropriate animal models to study pharmacological effects of 8beta-VE(2) in vivo. This prediction was confirmed in transactivation studies assessing estradiol (E(2)) and the two subtype-selective ligands on bovine ERbeta and on a series of hERalpha and hERbeta with mutations in their respective ligand-binding pockets. We have shown that the detailed understanding of the interactions of a compound with its target protein enables the identification of relevant species for pharmacological studies.
The doubly Cabibbo-suppressed decay D+ → K+ π− π+ (1997)

We report the observation of the doubly Cabibbo-suppressed decay D+ → K+ π− π+ in data from Fermilab charm hadroproduction experiment E791. With a signal of 59 ± 13 events we measured the ratio of the branching fraction for this mode to that of the Cabibbo-favored decay D+ → K− π+ π+ to be B(D+ → K+ π− π+) / B(D+ → K− π+ π+) = (7.7 ± 1.7 ± 0.8) × 10−3. A Dalitz plot analysis was performed to search for resonant structures.