gebhart/patrepeval huggingface dataset:
Clinical utility of biochemical analysis of cerebrospinal fluid (1995)

Abstract In addition to microbial culture, cytology, and immunological studies, physicians rely on the clinical chemistry laboratory for biochemical analysis of patients' cerebrospinal fluid (CSF). However, apart from routine glucose and protein determinations, the clinical value of other CSF analytes is often unclear. Here, we review the literature pertaining to the use of CSF biochemical measurements in managing patients with infectious disease, neoplasia, stroke and trauma, and dementia. Although a small number of studies demonstrate potential usefulness of some markers, we conclude that, without further study, the data are insufficient to support the routine clinical use of most of the analytes examined.
Direct measurement of the superconducting properties of single grain boundaries inY1Ba2Cu3O7−δ (1988)

We have made the first direct measurements of the critical current density of individual grain boundaries and their adjoining grains in ${\mathrm{Y}}_{1}$${\mathrm{Ba}}_{2}$${\mathrm{Cu}}_{3}$${\mathrm{O}}_{7\mathrm{\ensuremath{-}}\mathrm{\ensuremath{\delta}}}$ superconducting films. The critical current of the boundary was always found to be less than either of the two grains. The magnetic field dependence of the critical current of the grain boundaries indicates that they are comprised of regions of weak and strong Josephson coupling. A single grain boundary was also used to build and operate a simple dc SQUID. Current-voltage curves of a grain-boundary junction n the finite voltage range show subgap structure.
Rules for Anionic and Radical Ring Closure of Alkynes (2011)

This work reexamined the stereoelectronic basis for the "favored attack trajectories" regarding the nucleophilic and radical cyclizations of alkynes. In contrast to the original Baldwin rules, the acute attack angle of a nucleophile leading to the proposed endo-dig preference for the formation of small cycles is less favorable stereoelectronically than the alternative obtuse trajectory leading to the formation of exo-dig products. For smaller cycles, this intrinsic stereoelectronic preference can be masked by the greater thermodynamic stability of the less strained endo-products. Unbiased comparison of competing cyclization attacks has been accomplished via dissection of the activation barrier into the intrinsic barrier and thermodynamic component via Marcus theory. Intrinsic barriers of thermoneutral reactions strongly favor exo-dig closures, in full accord with the greater magnitude of two-electron bond forming interactions for the obtuse trajectory. This analysis agrees very well with experimental observations of efficient 3-exo-dig and 4-exo-dig cyclizations predicted to be unfavorable by the Baldwin rules and with the calculated 3-exo-/4-endo-, 4-exo-/5-endo-, and 5-exo-/6-endo-dig selectivities in the cyclizations of carbon-, nitrogen-, and oxygen-centered nucleophiles. The generality of these predictions is confirmed by analogous trends for the related radical cyclizations where the stereoelectronically favorable exo-closures are also preferred kinetically, with a few exceptions where a large difference in product stability skews the intrinsic stereoelectronic trends.
Tripartite functional assembly of a large class I aminoacyl tRNA synthetase (1992)

A 939-amino acid monomeric class I tRNA synthetase has been split into three inactive peptides. The three peptides spontaneously assemble in vivo to reconstitute active protein. Active tripartite complexes were demonstrated in vitro. The tripartite assembly of this synthetase increases by several-fold the size of a polypeptide that has been demonstrated to be assembled from more than two constituent pieces. The results indicate that contemporary single-chain tRNA synthetases or other large proteins could in principle develop from intermediates composed of non-covalent assemblages of multiple peptides.
<p>Single- and multiple-dose tolerability, safety, pharmacokinetics, and pharmacodynamics of the dual endothelin receptor antagonist aprocitentan in healthy adult and elderly subjects</p> (2019)

Aprocitentan was well tolerated in healthy subjects with a PK profile favorable for qd dosing.
Mucins Suppress Virulence Traits of Candida albicans (2014)

The yeast Candida albicans causes both superficial infections of the mucosa and life-threatening infections upon entering the bloodstream. However, C. albicans is not always harmful and can exist as part of the normal microbiota without causing disease. Internal body surfaces that are susceptible to infection by C. albicans are coated with mucus, which we hypothesize plays an important role in preventing infections. Here, we show that the main components of mucus, mucin glycoproteins, suppress virulence attributes of C. albicans at the levels of gene expression and the corresponding morphological traits. Specifically, mucins suppress attachment to plastic surfaces and human cells, the transition to cell-penetrating hyphae, and the formation of biofilms (drug-resistant microbial communities). Additionally, exposure to mucins induces an elongated morphology that physically resembles the mating-competent opaque state but is phenotypically distinct. We suggest that mucins are potent antivirulence molecules that have therapeutic potential for suppressing C. albicans infections.
Nest‐like Silicon Nanospheres for High‐Capacity Lithium Storage (2007)

Nest-like Si nanospheres and their highly reversible lithium storage (3952 mAh g–1 at 100 mA g–1) and excellent high-rate capability (3052 mAh g–1 at 2000 mA g–1) are reported (see figure). This result suggests that the as-prepared nest-like Si nanospheres are promising candidates as the anode materials of rechargeable Li-ion batteries. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2089/2007/c0621_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.
Specifications are (preferably) executable (1992)

The validation of specifications with respect to user requirements is extremely difficult. To ease the validation task and to give users immediate feedback on the behaviour of the future software, it was suggested that specifications should be made executable. However, Hayes and Jones [1] argue that executable specifications should be avoided because executability can restrict the expressiveness of specification langugages, and can adversely affect implementations. We argue for executable specifications by showing that non-executable formal specifications can be made executable on almost the same level of abstraction, and without essentially changing their structure. No new algorithms have to be introduced to get executability. Furthermore, we show that declarative specification languages combine high expressiveness and executability.
On the error vector magnitude as a performance metric and comparative analysis (2006)

In this paper, we present the error vector magnitude (EVM) as a figure of merit for assessing the quality of digitally modulated telecommunication signals. We define EVM for a common industry standard and derive the relationships among EVM, signal to noise ratio (SNR) and bit error rate (BER). We also compare among the different performance metrics and show that EVM can be equivalently useful as signal to noise ratio and bit error rate. A few simulation results are presented to illustrate the performance of EVM based on these relationships.
MYBPC3 mutations are associated with a reduced super-relaxed state in patients with hypertrophic cardiomyopathy (2017)

The "super-relaxed state" (SRX) of myosin represents a 'reserve' of motors in the heart. Myosin heads in the SRX are bound to the thick filament and have a very low ATPase rate. Changes in the SRX are likely to modulate cardiac contractility. We previously demonstrated that the SRX is significantly reduced in mouse cardiomyocytes lacking cardiac myosin binding protein-C (cMyBP-C). Here, we report the effect of mutations in the cMyBP-C gene (MYBPC3) using samples from human patients with hypertrophic cardiomyopathy (HCM). Left ventricular (LV) samples from 11 HCM patients were obtained following myectomy surgery to relieve LV outflow tract obstruction. HCM samples were genotyped as either MYBPC3 mutation positive (MYBPC3mut) or negative (HCMsmn) and were compared to eight non-failing donor hearts. Compared to donors, only MYBPC3mut samples display a significantly diminished SRX, characterised by a decrease in both the number of myosin heads in the SRX and the lifetime of ATP turnover. These changes were not observed in HCMsmn samples. There was a positive correlation (p < 0.01) between the expression of cMyBP-C and the proportion of myosin heads in the SRX state, suggesting cMyBP-C modulates and maintains the SRX. Phosphorylation of the myosin regulatory light chain in MYBPC3mut samples was significantly decreased compared to the other groups, suggesting a potential mechanism to compensate for the diminished SRX. We conclude that by altering both contractility and sarcomeric energy requirements, a reduced SRX may be an important disease mechanism in patients with MYBPC3 mutations.
An Evaluation of Hydroxyapatite and Biphasic Calcium Phosphate in Combination With Pluronic F127 and BMP on Bone Repair (2007)

Calcium phosphates like hydroxyapatite (HA), beta-tricalcium phosphate (beta-TCP), and their mixtures (biphasic calcium phosphates; BCP) are used clinically to repair bone defects. These materials can be difficult to handle and have no inherent biological activity. Handling properties of other bone substitute materials have been improved by combining them with an inert carrier such as Pluronic F-127 (Pluronic, BASF, Mt. Olive, NJ), while the addition of bone morphogenetic proteins (BMP) with such implants has also been shown to enhance bone repair. This study assessed the impact of adding Pluronic and BMPs to an HA (C-Graft) or a BCP (80/20 HA/beta-TCP ratio; Algisorb) implant's ability of promote bony repair in the rabbit calvarial defect model.Twenty-five New Zealand white rabbits were divided into 5 groups of 5 animals each. Bilateral calvarial defects were made in the parietal bones of each animal. HA or BCP alone or combined with Pluronic and/or BMP were implanted into the defect sites. Animals were euthanized at 6 weeks, postoperatively. Bone regeneration was evaluated quantitatively by histomorphometry. The amount of bone regeneration, which occurred in defects containing HA and BCP, was similar over the time period studied. Incorporating Pluronic increased handling and moldability without compromising osteoconductivity of either calcium phosphate. The addition of BMP significantly increased the amount of new bone formed with all calcium phosphates studied (P < 0.05). These results suggest that Pluronic can be added to calcium phosphates to enhance handling and moldability without any negative effects on their biocompatibility and that healing can be enhanced with the incorporation of BMPs.
Transforming growth factor‐α (1990)

In summary, although TGF-alpha was initially found in tumors, a number of later studies, some of them from the author's laboratory, have shown that TGF-alpha should no longer be considered a tumor associated growth factor. Rather, TGF-alpha is a normal physiological ligand for the EGF receptor. Table 2 lists some of the normal cellular sources of TGF-alpha. Our list is incomplete, but we know that TGF-alpha is made in keratinocytes and a number of epithelial cells, including gut and breast epithelial cells. It seems very likely that TGF-alpha is a major growth factor secreted by cells of epithelial origin. Zena Werb's and Russell Ross's groups have shown that activated macrophages make TGF-alpha. We have shown that brain makes TGF-alpha and Jeff Kudlow has found TGF-alpha made in the pituitary. Data from several sources, including David Lee, the author's laboratory, and Zena Werb's laboratory has shown that TGF-alpha is made during embryonic development. Therefore, it is now important to look at TGF-alpha in its normal physiological context. Finally, it should be stressed that, as was mentioned above, TGF-alpha is not necessarily a secreted growth factor 50 amino acids long. There is quite a bit of processing of the larger precursor that may or may not take place. This processing, which determines the ultimate size and location of the molecule, is also likely to influence its physiological action.
A VLSI sequencer chip for ATM traffic shaper and queue manager (2003)

To provide satisfactory quality of service (QOS) to all users in an asynchronous transfer mode (ATM) network, it is necessary to control the users' traffic so that network resources, such as transmission bandwidth and buffer capacity, can be efficiently and fairly utilized by all the users while still meeting the individual QOS requirement. It is proposed that users' traffic be controlled at two places in the network: at the user-network interface (UNI) by a traffic enforcer, and at the network-node interface (NNI) by a queue manager. Architectures for the traffic shaper and the queue manager are proposed. A key component, called the sequencer chip, to realize both architectures has been implemented, using a 1.2- mu m CMOS technology. It contains about 150 k transistors, has a die size of 7.5 mm*8.3 mm, and is packaged in a 223-pin ceramic pin grid array (PGA) carrier.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
NKp44, a Novel Triggering Surface Molecule Specifically Expressed by Activated Natural Killer Cells, Is Involved in Non–Major Histocompatibility Complex–restricted Tumor Cell Lysis (1998)

After culture in interleukin (IL)-2, natural killer (NK) cells acquire an increased capability of mediating non-major histocompatibility complex (MHC)-restricted tumor cell lysis. This may reflect, at least in part, the de novo expression by NK cells of triggering receptors involved in cytolysis. In this study we identified a novel 44-kD surface molecule (NKp44) that is absent in freshly isolated peripheral blood lymphocytes but is progressively expressed by all NK cells in vitro after culture in IL-2. Different from other markers of cell activation such as CD69 or VLA.2, NKp44 is absent in activated T lymphocytes or T cell clones. Since NKp44 was not detected in any of the other cell lineages analyzed, it appears as the first marker specific for activated human NK cells. Monoclonal antibody (mAb)-mediated cross-linking of NKp44 in cloned NK cells resulted in strong activation of target cell lysis in a redirected killing assay. This data indicated that NKp44 can mediate triggering of NK cell cytotoxicity. mAb-mediated masking of NKp44 resulted in partial inhibition of cytolytic activity against certain (FcgammaR-negative) NK-susceptible target cells. This inhibition was greatly increased by the simultaneous masking of p46, another recently identified NK-specific triggering surface molecule. These data strongly suggest that NKp44 functions as a triggering receptor selectively expressed by activated NK cells that, together with p46, may be involved in the process of non-MHC-restricted lysis. Finally, we show that p46 and NKp44 are coupled to the intracytoplasmic transduction machinery via the association with CD3zeta or KARAP/DAP12, respectively; these associated molecules are tyrosine phosphorylated upon NK cell stimulation.
Epinephrine suppresses rap1B.GAP-activated GTPase activity in human platelets. (1992)

Lysate from quiescent platelets promotes rapid hydrolysis of [gamma-32P]GTP bound to rap1B. Various platelet agonists, including platelet-activating factor, phorbol 12,13-dibutyrate, alpha-thrombin, epinephrine, ADP, and iloprost, that affect platelet metabolism by different signal transduction pathways were used to stimulate intact platelets and study their effects on rap1B.GAP-activated GTPase activity (GAP, GTPase-activating protein). Only epinephrine was found to dramatically decrease not only the rate but also the amount of hydrolysis of rap1B-bound GTP activated by rap1B.GAP. This effect was dose dependent and occurred rapidly. The suppression of GTPase activity was specific for rap1B.GAP in that ras.GAP- and rap2B.GAP-activated GTPase activity were not affected by epinephrine stimulation. This effect appears to be mediated by the alpha 2-adrenergic receptor, as evidenced by a similar suppression of GTPase activity by stimulating platelets with the synthetic alpha 2-adrenergic receptor agonist UK14304 (bromoxidine). Furthermore, the selective alpha 2-adrenergic receptor antagonist yohimbine blocked the suppression of GTPase activity expressed in epinephrine-stimulated cell lysates. No apparent changes in the patterns of protein expression or tyrosine phosphorylation were observed. Although the migration characteristics upon anion-exchange chromatography of rap1B.GAP and ras.GAP activities were unaffected by epinephrine stimulation, the specific activity of rap1B.GAP was noticeably decreased with 250 and 500 microM epinephrine. These results suggest a possible role for rap1B and rap1B.GAP in epinephrine-stimulated signal transduction.
Comparative Study of PLL, DDS and DDS-based PLL Synthesis Techniques for Communication System (2010)

The phase locked loop(PLL) has been widely used in wireless communication systems due to the high frequency resolution and the short locking time. The Direct Digital Synthesis(DDS) is also an emerging and maturing signal generation technology. But another advanced technique in which, DDS signal is mixed with the voltage-control oscillator output in the PLL feedback path. This solution helps in avoiding some of the typical tradeoffs in PLL. In particular, it is possible to achieve a very high-frequency resolution together with fast settling and spectral purity. The proposed design consists in describing the mixed behavior of this DDS-based PLL architecture starting from the specifications of each building block. The HDL models of critical PLL blocks have been described in VHDL-AMS to predict the different specifications of the PLL. The effect of different noise sources has been efficiently introduced to study the system performance. The obtained results are composed with transistor-level simulations to validate the effectiveness of the proposed models. The comparative study showed the performances of different parameters. Finally, DDS- based PLL architecture is better than other architectures.
Nonencapsulated Haemophilus influenzae in Aboriginal infants with otitis media: prolonged carriage of P2 porin variants and evidence for horizontal P2 gene transfer (1997)

Aboriginal infants in the Northern Territory of Australia experience recurrent otitis media from an early age. Nonencapsulated Haemophilus influenzae (NCHi) colonization of the nasopharynx initially occurs within weeks of birth, persists throughout infancy and most of childhood, and contributes to otitis media. We established previously that the high carriage rates of NCHi in these infants result from concurrent and successive colonization with multiple strains, with sequential elimination of dominant strains. We have now sequenced loops 4, 5, and 6 of the NCHi P2 porin gene and characterized several strains with prolonged carriage times. Furthermore, despite a wide diversity of P2 gene sequences, we have four examples of P2 gene identity for strains with different genetic backgrounds as characterized by PCR ribotyping and randomly amplified polymorphic DNA typing, which leads us to suggest that the P2 gene has been transferred between strains. We also discuss the possibility that the paradoxical observation of cocolonization and prolonged carriage of P2-identical strains is related to immune suppression or tolerance in the host.
BibA: a novel immunogenic bacterial adhesin contributing to group B Streptococcus survival in human blood (2006)

By the analysis of the recently sequenced genomes of Group B Streptococcus (GBS) we have identified a novel immunogenic adhesin with anti-phagocytic activity, named BibA. The bibA gene is present in 100% of the 24 GBS strains analysed. BibA-specific IgG were found in human sera from normal healthy donors. The putative protein product is a polypeptide of 630 amino acids containing a helix-rich N-terminal domain, a proline-rich region and a canonical LPXTG cell wall-anchoring domain. BibA is expressed on the surface of several GBS strains, but is also recovered in GBS culture supernatants. BibA specifically binds to human C4-binding protein, a regulator of the classic complement pathway. Deletion of the bibA gene severely reduced the capacity of GBS to survive in human blood and to resist opsonophagocytic killing by human neutrophils. In addition, BibA expression increased the virulence of GBS in a mouse infection model. The role of BibA in GBS adhesion was demonstrated by the impaired ability of a bibA knockout mutant strain to adhere to both human cervical and lung epithelial cells. Furthermore, we calculated that recombinant BibA bound to human epithelial cells of distinct origin with an affinity constant of approximately 10(-8) M for cervical epithelial cells. Hence BibA is a novel multifunctional protein involved in both resistance to phagocytic killing and adhesion to host cells. The identification of this potential new virulence factor represents an important step in the development of strategies to combat GBS-associated infections.
Rods, tori, and honeycombs: the directed self‐assembly of microtissues with prescribed microscale geometries (2007)

It is thought that, due to energy and surface area:volume minimization, the spheroid is the terminal structure of cellular self-assembly. We investigated whether self-assembly could be directed to generate complex-shaped structures. Using micromolded, nonadhesive agarose hydrogels seeded with rat hepatoma (H35s), human fibroblasts (NHFs), or their mix (1:1), we show that cells can self-assemble rods, tori, and honeycombs. We found that in trough-shaped recesses up to 2.2 mm long, H35s readily formed rod-like structures stable at 49% the recess lengths. They also formed intact tori (88%) and fully intact honeycombs structures with patent lumens (9/9) even when released from the mold. In contrast, NHFs in trough features progressed rapidly to spheroids and formed fewer stable tori (30%) and honeycombs (0/9). The 1:1 mix of cells self-assembled rapidly like NHFs but were able to form more stable structures (tori: 30%, honeycombs: 3/9). Experiments with labeled cells in tori and honeycombs revealed that cells self-segregated in these complex structures, with H35s enveloping NHFs, and that NHFs had different morphologies in taut vs. relaxed structures. These data open new possibilities for in vitro tissue models for embryo- and organogenesis study as well as for tissue engineering applications.