gebhart/patrepeval huggingface dataset:
Molecular modification of anticholinergics as probes for muscarinic receptors. 3. Conformationally restricted analogs of benactyzine (1987)

The synthesis and pharmacological evaluation of conformationally restricted analogues of certain anticholinergic agents is a powerful method for probing the topography of the muscarinic receptor. In the present study, clues as to the binding conformation of structurally flexible anticholinergics are provided by approximating certain conformations of benactyzine by synthetic analogues 1-6, which are structurally locked into desired conformations. The pharmacological activity of each analogue is an indication of how well particular conformational models are accommodated by the receptor. The conformation of benactyzine in which an intramolecular hydrogen bond may exist between the hydroxyl group and the carbonyl oxygen of the ester group (conformation I) is approximated by the synthetic analogue 2,2-diphenyl-3-tetrahydrofuranyl (diethylamino)ethyl ether (1) and related analogues. Pharmacological evaluation using dose-response experiments on isolated rat ileum tissue demonstrated that these compounds noncompetitively inhibited acetylcholine-induced ileum contractions. Restriction of the conformational freedom of the amino side chain of 1 by synthesis of the hexahydro[3,4-b]furan derivative 3 provided a weak but competitive inhibitor at low concentration. The conformation of benactyzine in which an intramolecular hydrogen bond may exist between the hydroxyl group and the ether oxygen of the ester group (conformation II) is approximated by 2,2-diphenyl-4-[2-(diethylamino)ethyl]-3-tetrahydrofuranone (4). Pharmacological studies showed that this compound competitively inhibited acetylcholine-induced ileum contractions. These experiments provide evidence that receptor-bound conformation II for benactyzine is preferred over conformation I in providing competitive binding with the muscarinic receptor.
Nanogel-Based PspA Intranasal Vaccine Prevents Invasive Disease and Nasal Colonization by Streptococcus pneumoniae (2020)

ABSTRACT To establish a safer and more effective vaccine against pneumococcal respiratory infections, current knowledge regarding the antigens common among pneumococcal strains and improvements to the system for delivering these antigens across the mucosal barrier must be integrated. We developed a pneumococcal vaccine that combines the advantages of pneumococcal surface protein A (PspA) with a nontoxic intranasal vaccine delivery system based on a nanometer-sized hydrogel (nanogel) consisting of a cationic cholesteryl group-bearing pullulan (cCHP). The efficacy of the nanogel-based PspA nasal vaccine (cCHP-PspA) was tested in murine pneumococcal airway infection models. Intranasal vaccination with cCHP-PspA provided protective immunity against lethal challenge with Streptococcus pneumoniae Xen10, reduced colonization and invasion by bacteria in the upper and lower respiratory tracts, and induced systemic and nasal mucosal Th17 responses, high levels of PspA-specific serum immunoglobulin G (IgG), and nasal and bronchial IgA antibody responses. Moreover, there was no sign of PspA delivery by nanogel to either the olfactory bulbs or the central nervous system after intranasal administration. These results demonstrate the effectiveness and safety of the nanogel-based PspA nasal vaccine system as a universal mucosal vaccine against pneumococcal respiratory infection.
Synthesis of Polyphenylenes via Bergman Cyclization of Enediyne Monomers (1993)

Abstract : Described is the synthesis of polyphenylenes via the Bergman cyclization of enediyne monomers. These monomers were synthesized via the Stephans-Castro/Sonogashira reaction and polymerized under varying conditions.
The Impact of Chiral Citronellyl‐Functionalization on Indolenine and Anilino Squaraine Thin Films (2021)

Abstract The impact on chiral aggregation in solution processed and thermally annealed thin films of two indolenine and one anilino squaraines with chiral ( S )‐citronellyl functionalization at the nitrogen of the squaraine backbone is investigated. A pseudo polymorphic crystal structure is obtained for one of the indolenine squaraines, but thin films of both compounds are basically non‐aggregated and truly isotropic as evidenced by spectroscopic ellipsometry. The anilino squaraine coalesces and readily aggregates to circular dichroic but discontinuous thin films. The extent of circular dichroism correlates with the morphology of the samples, which is quantified by Mueller matrix polarimetry in combination with atomic force microscopy. The shape of the CD spectra reinforces the hybrid Frenkel and charge‐transfer excitonic nature of the characteristic double hump signatures within unpolarized absorbance spectra of previously investigated non‐chiral anilino squaraines with linear alkyl chain functionalization. Such excitonic CD offers an additional design parameter for next‐generation opto‐electronic devices.
Gradient Coding with Iterative Block Leverage Score Sampling (2023)

We generalize the leverage score sampling sketch for $\ell_2$-subspace embeddings, to accommodate sampling subsets of the transformed data, so that the sketching approach is appropriate for distributed settings. This is then used to derive an approximate coded computing approach for first-order methods; known as gradient coding, to accelerate linear regression in the presence of failures in distributed computational networks, \textit{i.e.} stragglers. We replicate the data across the distributed network, to attain the approximation guarantees through the induced sampling distribution. The significance and main contribution of this work, is that it unifies randomized numerical linear algebra with approximate coded computing, while attaining an induced $\ell_2$-subspace embedding through uniform sampling. The transition to uniform sampling is done without applying a random projection, as in the case of the subsampled randomized Hadamard transform. Furthermore, by incorporating this technique to coded computing, our scheme is an iterative sketching approach to approximately solving linear regression. We also propose weighting when sketching takes place through sampling with replacement, for further compression.
A Long History of Supercomputing (2016)

As part of its national security science mission, Los Alamos National Laboratory and HPC have a long, entwined history dating back to the earliest days of computing. From bringing the first problem to the nation’s first computer to building the first machine to break the petaflop barrier, Los Alamos holds many “firsts” in HPC breakthroughs. Today, supercomputers are integral to stockpile stewardship and the Laboratory continues to work with vendors in developing the future of HPC.
Highly Atom-Economic One-Pot Formation of Three Different C−P Bonds:  General Synthesis of Acyclic Tertiary Phosphine Sulfides (2005)

The reaction of benzothiadiphosphole 1 with an equimolar mixture of R1MgBr and R2MgBr gave intermediate A', which, after only 4-5 min, was treated with an equimolar amount of R3MgBr, giving the asymmetric phosphine PR1R2R3 in 45% overall yield (75-80% yield when R1 = R2 and 85-90% yield when R1 = R2 = R3) and the byproduct 6 in 90% yield. The treatment of 6 with PCl3 quantitatively regenerates the starting reagent 1. Treatment of the phosphines with elemental sulfur gave the corresponding sulfides.
Thermal Dissociation of Multimeric Protein Complexes by Using Nanoelectrospray Mass Spectrometry (2003)

The behavior of macromolecular systems at different temperatures is often crucial to their biological activity and function. While heat-induced changes of individual proteins are readily monitored by a number of spectroscopic methods, changes in noncovalent complexes of biomolecules are more challenging to interpret. Nanoelectrospray mass spectrometry is becoming increasingly powerful in the study of large noncovalent complexes, and here we describe the design, characterization, and application of a novel probe that allows the thermocontrol of the solution in the electrospray capillary. The transition temperature for the unfolding of the protein lysozyme is readily obtained and correlates closely with that measured by fluorescence spectroscopy, thereby demonstrating the validity of this approach. We apply this technique to the study of the 200-kDa complex of the small heat shock protein TaHSP16.9, revealing both its dissociation into suboligomeric species and an increase in its size and polydispersity at elevated temperatures. In contrast, gas-phase activation of this complex is also carried out and yields a dissociation pathway fundamentally different from that observed for thermal activation in solution. As such, this probe allows the study of the reversible heat-induced changes of noncovalent complexes in a biologically relevant manner.
Multidimensional Cauchy method and adaptive sampling for an accurate microwave circuit modeling (1998)

This paper presents an effective generic approach for computer-aided design of microwave circuits. We extend the one-dimensional Cauchy method for frequency-response interpolation to a multidimensional Cauchy interpolation, with respect to both frequency and physical dimensions. This paper also demonstrates the feasibility of applying adaptive sampling to the multidimensional rational-function expansion. Three examples, including optimization and Monte Carlo analysis, have been given to verify the validity of the proposed approach.
PCR biocompatibility of lab-on-a-chip and MEMS materials (2007)

DNA amplification using the polymerase chain reaction (PCR) is an important tool in biotechnology, pathogen surveillance in food, medical and forensic science etc. The PCR technique is now an important part of the research in and development of miniaturized biochemical analysis systems. However, reduced or no DNA amplification at all is an important challenge for microfabricated PCR devices due to a negative interaction between PCR chemicals and the surrounding environment, i.e. the materials encapsulating the PCR mix. Materials of special interest regarding PCR compatibility are silicon, glass and polymers, which are important in the fabrication of microelectromechanical systems (MEMS), micro total analysis systems (µTAS) and lab-on-a-chip (LOC) systems. The PCR inhibition effect is a particularly important phenomenon in microsystems due to an increased surface-to-volume ratio which enhances the possibility of interaction between the surfaces and ingredients in the PCR mixture. By proper surface treatment the PCR reaction can be facilitated and in this paper we present a systematic and quantitative study of the impact on the PCR compatibility of a chemical and a biological surface treatment. The chemical treatments are based on the silanizing agent dichlordimethylsilane [(CH3)2SiCl2]], while the biological treatment is based on the protein bovine serum albumin (BSA). We present a simple model system for the investigation of the PCR compatibility of three widely used materials in microfabrication, namely silicon, glass and SU-8. The impact on PCR performance, measured by means of PCR efficiency, of untreated as well as chemically and biologically treated materials is studied. We show a convenient method of assessing the PCR compatibility of silicon, glass and SU-8 with a degree of information not presented before.
An Adaptive Guidance Approach for Spinning Projectiles (2004)

Previous work1 has shown a significant potential for improving the accuracy of direct fire spinning projectiles through the implementation of aerodynamic control. A guidance law optimized for this application was developed. Further research has shown that the guidance law cannot adjust quickly enough to accommodate actuator nonlinearities and uncertainties. Of particular interest is the use of miniature synthetic jets, which achieve a control force by interacting with the flow. The full model of such actuators might not be completely known leading to decreased controlled system performance. Actuator induced moment effect causes amplification or attenuation of the control force depending on the moment direction causing increased target misses and peak control force. Wind disturbances are expected to cause further performance degradation. We describe and provide a preliminary evaluation of a method of dealing with these problems by augmenting the guidance law with an adaptive controller. Copyright © 2004 by Georgia Institute of Technology.
ChemInform Abstract: Synthesis and Reactivity of Ruthenium Complexes with Dibenzothiophene and Hexahydrodibenzothiophene Ligands: Models for Catalytic Hydrodesulfurization. (1990)

Abstract As models for the adsorption of dibenzothiophene (II) and hexahydrodibenzothiophene on hydrodesulfurization catalysts, the complex (III), its hexahydrodibenzothiophene analogue (yield 65%), and the binuclear analogue (VI) (54%) are prepared.
Control of Synapse Number by Glia (2001)

Although astrocytes constitute nearly half of the cells in our brain, their function is a long-standing neurobiological mystery. Here we show by quantal analyses, FM1-43 imaging, immunostaining, and electron microscopy that few synapses form in the absence of glial cells and that the few synapses that do form are functionally immature. Astrocytes increase the number of mature, functional synapses on central nervous system (CNS) neurons by sevenfold and are required for synaptic maintenance in vitro. We also show that most synapses are generated concurrently with the development of glia in vivo. These data demonstrate a previously unknown function for glia in inducing and stabilizing CNS synapses, show that CNS synapse number can be profoundly regulated by nonneuronal signals, and raise the possibility that glia may actively participate in synaptic plasticity.
HLA ALLOANTIBODIES IN LUNG TRANSPLANTATION (1999)

685 There have been numerous reports describing risk in kidney and heart transplantation associated with anti-HLA antibodies in the recipient. In lung transplantation this issue is less clear, perhaps because lung patients are less likely to be presensitized. We examined 147 lung transplants, 75 males and 72 females, performed at this institution to examine whether or not HLA sensitization influenced outcome. Lymphocytotoxic T cell PRA's (CPRA) were generally low with only 11 patients (7.5%) having a PRA>10%. We also examined the patients pre-transplant (pre-TX) sera using a more sensitive flow cytometric method (FPRA) that utilized purified HLA class I antigens attached to beads (FlowPRA I, One Lambda Inc.). Using this methodology, more females (43.1%) had FPRA's>10% than males (26.7%, p=0.04). In addition, 7 females (13.2%) and 5 males (8.5%) had positive retrospective T cell flow cytometric crossmatches (FCXM). One year actuarial graft survivals are shown in the table.TableCPRA's >10% did not influence outcome overall or in males, however sensitized females had 30% lower graft survival than did nonsensitized females. The FPRA methodology did not predict outcome. A positive pre-TX FCXM was associated with lower survival only in females. Post-TX FCXM results were available in 58 patients. Again a positive reaction was associated with lower graft survival in only female patients. While the relatively small number of transplants studied prevents drawing definitive conclusions, it does seem that HLA sensitization does have a negative impact on outcome at least in female lung transplant recipients. As it is often difficult to obtain pre-TX crossmatches, approaches to desensitize female patients pre-TX might diminish the risk.
Recent Advances of Bismuth(III) Salts in Organic Chemistry: Application to the Synthesis of Aliphatics, Alicyclics, Aromatics, Amino Acids and Peptides, Terpenes and Steroids of Pharmaceutical Interest (2009)

In this review recent uses of the inexpensive and commercially available bismuth(III) salts in organic chemistry will be highlighted. Their application to the development of new processes or synthetic routes that lead to compounds of pharmaceutical interest will be matter of discussion. It will focus on bismuth(III) salt-mediated reactions involving the preparation of non-heterocyclic compounds such as aliphatics and alicyclics, monocyclic and polycyclic aromatics, amino acids and peptides, terpenes and steroids.
Age and Radiation Response in Glioblastoma Multiforme (2001)

Older GM patients are less likely to have good responses to postoperative external beam radiation therapy. Karnofsky Performance Scale score before radiation treatment and extent of surgical resection are additional predictors of radiographically assessed radiation response in GM.
Time-frequency representations of auditory signatures: Dynamic signal models (1992)

Signal theory provides a mathematical framework within which to pose questions of representation. Such theory establishes the minimum conditions for which signals can be represented uniquely, for example. Time-frequency distributions are often used as representations of the temporally varying spectral characteristics of acoustic signals. When one desires a correspondence between the distribution of a signal and the auditory perception of that signal, however, it is not clear how to proceed. Several researchers have approached the auditory representation problem within the domain of time-frequency distributions [M. D. Riley, SpeechTime-FrequencyRepresentations (Kluwer Academic, Boston, 1989) and W. Heinbach, Acustica 67, 113–121 (1988)]. In the present paper, an alternative approach is provided based on dynamic signal models and psychoacoustic spectral processing theory. This approach is applied to characterizing acoustic transients such as automotive starter sounds. A dynamic signal model is introduced and experimental results are presented concerning the ability of this model to uniquely characterize the signals of interest. Application of Terhardt’s Fourier t transform is also investigated [E. Terhardt, Acustica 57, 242–256 (1985)] and results are compared with other time-frequency distributions. [Work supported by a Bell Communications Research graduate fellowship, the Ford Motor Company, and a National Science Foundation PYI award.]
Assessment of variability in cerebral vasculature for neuro-anatomical surgery planning in rodent brain (2011)

Clinical and pre-clinical studies show that deep brain stimulation (DBS) of targeted brain regions by neurosurgical techniques ameliorate psychiatric disorder such as anorexia nervosa. Neurosurgical interventions in preclinical rodent brain are mostly accomplished manually with a 2D atlas. Considering both the large number of animals subjected to stereotactic surgical experiments and the associated imaging cost, feasibility of sophisticated pre-operative imaging based surgical path planning and/or robotic guidance is limited. Here, we spatially normalize vasculature information and assess the intra-strain variability in cerebral vasculature for a neurosurgery planning. By co-registering and subsequently building a probabilistic vasculature template in a standard space, we evaluate the risk of a user defined electrode trajectory damaging a blood vessel on its path. The use of such a method may not only be confined to DBS therapy in small animals, but also could be readily applicable to a wide range of stereotactic small animal surgeries like targeted injection of contrast agents and cell labeling applications.
Waveguide demultiplexer based on Helmholtz-resonator mediated extraordinary acoustic transmission (2022)

The design of an acoustic demultiplexer based on in-line Helmholtz resonators is demonstrated analytically via a modified transfer matrix method and computationally through finite element simulations. The modeled system consists of a single input waveguide that splits in a Y-configuration into two output waveguides. Each output arm has a single tuned Helmholtz resonator embedded in-line along the length of the guide. The Helmholtz resonators in each arm consist of a single cavity with two necks—one directed towards the input and output sides of the guide. The phenomenon of extraordinary acoustic transmission results in near perfect transmission of sound along each output arm in a small frequency interval about the Helmholtz resonant frequency. The demultiplexed frequencies are determined by the physical dimensions of the Helmholtz resonator. Using a single Helmholtz resonator in each output arm means that the system is more compact compared to other proposed schemes using either side-loaded Helmholtz resonators or stubs.
ChemInform Abstract: CHEMISTRY OF HETEROCYCLIC COMPOUNDS. 23. SYNTHESIS OF MULTIHETEROMACROCYCLES POSSESSING 2,6‐PYRIDINO SUBUNITS CONNECTED BY CARBON‐OXYGEN LINKAGES (1977)

Abstract Die Umsetzung von 2‐Brom‐pyridin (I) mit Natrium‐äthoxyäthylat (II) liefert das Substitutionsprodukt (III).
Combination of Photodynamic Therapy and Specific Immunotherapy Efficiently Eradicates Established Tumors (2015)

We show that immunotherapy can be efficiently combined with PDT to eradicate established tumors, based on strong local tumor ablation and the induction of a robust systemic immune response. These results suggest combination of active immunotherapy with tumor ablation by PDT as a feasible novel treatment strategy for advanced cancer.
Abemaciclib plus fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in premenopausal women: subgroup analysis from the MONARCH 2 trial (2021)

NCT02107703. Registered April 08, 2014- Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02107703 .
Semistructured data and XML (2002)

This paper argues that the research on semistructured data is receiving a new set of challenges with the advent of XML (Extensible Mark-up Language [Bos97, Con98]). This is a new standard approved by the World Wide Web Consortium that many believe will become the de facto data exchange format for the Web. XML supports the electronic exchange of machine-readable data (while HTML is designed primarily for human-readable documents). XML data shares many features of semistructured data: its structure can be irregular, is not always known ahead of time, and may change frequently and without notice. On the other hand it is easy to convert data from any source into XML which will make it attractive for organizations to &amp;quot;publish&amp;quot; their information sources in XML, and thus make them available to other XML applications on the Web. For XML applications to reach their full potential however, we need to build the right tools to process data in this new format. Existing Web tools (browsers, search engines) are oriented toward document operations . For XML we need database operations , like data extraction, data integration, data translation, data storage. The research done so far on semistructured data may offer some solutions to the database problems posed by XML. For example the recently proposed query language for XML, called XML-QL [DFF
Adaptive Optics for Brillouin Micro-Spectroscopy (2018)

Brillouin spectroscopy is a powerful optical technique for non-contact viscoelastic characterizations enabling three-dimensional mapping of biological samples. Here we present an adaptive-optics configuration for Brillouin spectroscopy providing 2.5-fold enhancement in Brillouin signal strength and 1.4-fold improvement in axial resolution by correcting for sample induced aberrations.