gebhart/patrepeval huggingface dataset:
Immunogenicity of stabilized HIV-1 Env trimers delivered by self-amplifying mRNA (2021)

Self-amplifying mRNA (saRNA) represents a promising platform for nucleic acid delivery of vaccine immunogens. Unlike plasmid DNA, saRNA does not require entry into the nucleus of target cells for expression, having the capacity to drive higher protein expression compared to mRNA as it replicates within the cytoplasm. In this study, we examined the potential of stabilized native-like HIV-1 Envelope glycoprotein (Env) trimers to elicit immune responses when delivered by saRNA polyplexes (PLXs), assembled with linear polyethylenimine. We showed that Venezuelan equine encephalitis virus (VEEV) saRNA induces a stronger humoral immune response to the encoded transgene compared to Semliki Forest virus saRNA. Moreover, we characterized the immunogenicity of the soluble and membrane-bound ConSOSL.UFO Env design in mice and showed a faster humoral kinetic and an immunoglobulin G (IgG)2a skew using a membrane-bound design. The immune response generated by PLX VEEV saRNA encoding the membrane-bound Env was then evaluated in larger animal models including macaques, in which low doses induced high IgG responses. Our data demonstrated that the VEEV saRNA PLX nanoparticle formulation represents a suitable platform for the delivery of stabilized HIV-1 Env and has the potential to be used in a variety of vaccine regimens.
Managing Data Quality Risk in Accounting Information Systems (2011)

The quality of data contained in accounting information systems has a significant impact on both internal business decision making and external regulatory compliance. Although a considerable body of literature exists on the issue of data quality, there has been little research done at the task level of a business process to develop effective control strategies to mitigate data quality risks. In this paper, we present a methodology for managing the risks associated with the quality of data in accounting information systems. This methodology first models the error evolution process in transactional data flow as a dynamical process; it then finds optimal control policies at the task level to mitigate the data quality-related risks using a Markov decision process model with risk constraints. The proposed Markov decision methodology facilitates the modeling of multiple dimensions of error dependence, captures the correlated impact among control procedures, and identifies an optimal control policy. A revenue realization process of an international production company is used to illustrate this methodology.
Characterisation of Five Missense Mutations in the Cystathionine Beta-Synthase Gene from Three Patients with B(6)-Nonresponsive Homocystinuria (1997)

Homocystinuria, due to a deficiency of the enzyme cystathionine β-synthase (CBS), is an inborn error of sulphur-amino acid metabolism. This is an autosomal recessive disease which results in hyperhomocysteinaemia and a wide range of clinical features, including optic lens dislocation, mental retardation, skeletal abnormalities and premature thrombotic events. We report the identification of 5 missense mutations in the protein-coding region of the CBS gene from 3 patients with pyridoxine-nonresponsive homocystinuria. Reverse- transcription PCR was used to amplify CBS cDNA from each patient and the coding region was analysed by direct sequencing. The mutations detected included 3 novel (1058C→T, 992C→A and 1316G→A) and 2 previously identified (430G→A and 833C→T) base alterations in the CBS cDNA. Each of these mutations predicts a single amino acid substitution in the CBS polypeptide. Appropriate cassettes of patient CBS cDNA, containing each of the above defined mutations, were used to replace the corresponding cassettes of normal CBS cDNA sequence within the bacterial expression vector pT7-7. These recombinant mutant and normal CBS constructs were expressed in Escherichia coli cells and the catalytic activities of the mutant proteins were compared with normal. All of the mutant proteins exhibited decreased catalytic activity in vitro, which confirmed the association between the individual mutation and CBS dysfunction in each patient.
Crucial role of tumor necrosis factor (TNF) receptor 2 and membrane‐bound TNF in experimental cerebral malaria (1997)

Tumor necrosis factor (TNF) has been implicated in the pathogenesis of experimental cerebral malaria (CM), but the respective role of its two types of receptors has not been established. A significant increase in the expression of TNF-receptor 2 (TNFR2, p75), but not of TNFR1 (p55), was found on brain microvessels at the time of CM in susceptible animals. Moreover, mice genetically deficient for TNFR2 (Tnfr2null) were significantly protected from experimental CM, in contrast to TNFR1-deficient (Tnfr1null) mice, which were as susceptible as wild-type mice. To identify the factors involved in the protection from CM conferred by the lack of TNFR2, we assessed in both knockout and control mice the serum concentrations of mediators that are critical for the development of CM, as well as the up-regulation of intercellular adhesion molecule-1 (ICAM-1) in the brain microvessels. No significant difference in serum levels of TNF and interferon-gamma was found between infected wild-type and Tnfr1null or Tnfr2null mice. Interestingly, the pronounced ICAM-1 up-regulation and leukocyte sequestration, typically occurring in brain microvessels of CM-susceptible animals, was detected in infected control and Tnfr1null mice-both of which developed CM-whereas no such ICAM-1 up-regulation or leukocyte sequestration was observed in Tnfr2null mice, which were protected from CM. Making use of microvascular endothelium cells (MVEC) isolated from wild-type, Tnfr1null or Tnfr2null mice, we show that soluble TNF requires the presence of both TNF receptors, whereas membrane-bound TNF only needs TNFR2 for TNF-mediated ICAM-1 up-regulation in brain MVEC. Thus, only in MVEC lacking TNFR2, neither membrane-bound nor soluble TNF cause the up-regulation of ICAM-1 in vitro. In conclusion, these results indicate that the interaction between membrane TNF and TNFR2 is crucial in the development of this neurological syndrome.
Advanced Continuous Flow Platform for On‐Demand Pharmaceutical Manufacturing (2018)

As a demonstration of an alternative to the challenges faced with batch pharmaceutical manufacturing including the large production footprint and lengthy time-scale, we previously reported a refrigerator-sized continuous flow system for the on-demand production of essential medicines. Building on this technology, herein we report a second-generation, reconfigurable and 25 % smaller (by volume) continuous flow pharmaceutical manufacturing platform featuring advances in reaction and purification equipment. Consisting of two compact [0.7 (L)×0.5 (D)×1.3 m (H)] stand-alone units for synthesis and purification/formulation processes, the capabilities of this automated system are demonstrated with the synthesis of nicardipine hydrochloride and the production of concentrated liquid doses of ciprofloxacin hydrochloride, neostigmine methylsulfate and rufinamide that meet US Pharmacopeia standards.
Modification of primary and recurrent genital herpes in guinea pigs by passive immunization (2002)

Guinea pigs were administered antiserum 24 h (As+24) or 72 h (As+72) after intravaginal herpes simplex virus type 2 (HSV-2) challenge. Treatment at either time reduced acute virus replication in the dorsal root ganglia and the overall magnitude of replication in the genital tract. In two studies, As+24 treatment significantly reduced the severity of primary genital skin disease and the frequency of subsequent spontaneous recurrent disease. In contrast, As+72 treatment produced a modest reduction in primary disease severity but did not impact on recurrent disease. Quantitative PCR analysis of dorsal root ganglia DNA from latently infected animals showed that As+24 treatment produced a significantly reduced viral DNA burden, which appeared to correlate with the reduction in recurrent disease. The amount of DNA in the ganglia of As+72-treated animals was not significantly lower than that of controls. These observations have implications for both the dynamics of latency establishment and desirable vaccine characteristics.
Microencapsulation of Leydig Cells: A System for Testosterone Supplementation (2003)

The use of testosterone supplementation for elderly men has increased markedly over the last decade due to a recognized gradual decline in serum testosterone, which may lead to decreased bone mass, muscle strength, and libido. Testosterone supplementation is also used widely to treat some forms of erectile dysfunction, androgen deficiency, and infertility. However, long-term exogenous testosterone therapy has been associated with several complications, such as fluid retention, nitrogen retention, and hypertension. Due to these problems, alternate treatment modalities, involving more physiological and longer-acting systems for androgen delivery, have been pursued. Alginate-poly-L-lysine-encapsulated Leydig cell microspheres were used as a novel method for the delivery of testosterone in vivo. Encapsulated Leydig cells, which were stimulated with human chorionic gonadotropin, secreted high levels of testosterone in culture. Unencapsulated cells injected i.p. or s.c. failed to produce any testosterone levels, even with human chorionic gonadotropin stimulation. Castrated rats that were administered encapsulated Leydig cells i.p. or s.c. maintained a serum testosterone level between 0.23 and 0.51 ng/ml. Similar levels of testosterone were obtained for 43 d when the encapsulated Leydig cells were injected s.c. (0.28-0.48 ng/ml). Approximately 10% of a normal adult rat Leydig cell population was injected into each castrated animal; however, this resulted in serum testosterone levels of up to 40% of normal. Clinically, testosterone is usually delivered for supplementation and not for full replacement therapy. Therefore, the findings of this study suggest that microencapsulated Leydig cells may be a viable option as a therapeutic modality involving testosterone supplementation.
Sonochemical preparation and properties of nanostructured palladium metallic clusters (1998)

Nanoscale particles of palladium metallic clusters have been prepared at room temperature by sonochemical reduction of a 1:2 molar mixture of palladium acetate, Pd(O2CCH3)2 , and myristyltrimethylammonium bromide, CH3(CH2)12N(CH3)3Br (NR4X), in tetrahydrofuran (THF) or methanol. Apart from its stabilizing effect, NR4X acts as a reducing agent, probably due to the decomposition that occurs at the liquid-phase region immediately surrounding the collapsing cavity, and provides reducing radicals. Addition of 0.2 m ethanol–methanol in the THF process enhances the sonochemical reduction of PdII because of its highly volatile nature producing various reducing radicals inside the collapsing bubble. Analyses by UV–VIS spectroscopy indicated the initial formation of a PdII–NR4X complex, which, in turn, reduced to Pd0 . Elemental analysis of the resulting solid (sonication residue) shows that the THF process yields NR4X stabilized-palladium clusters, whereas the methanol process shows the formation of pure Pd agglomerates. X-Ray diffraction (XRD) and transmission electron microscopy (TEM) with selected area electron diffraction (SAED) techniques were carried out to ascertain the nature, size and morphology of the Pd clusters. TEM of NR4X stabilized-Pd shows the presence of spherical particles of 10–20 nm in size. Selected area electron diffraction (SAED), along with TEM, reveals that the pure Pd consists of dense agglomerates, whereas NR4X stabilized-Pd exists as thin crystallites. These Pd nanoclusters are catalytically active towards carbon–carbon coupling, or Heck reaction, in the absence of phosphine ligands, to a moderate extent of 30% conversion. Hydrogenation of cyclohexene to cyclohexane has also been studied using sonochemically generated Pd materials. The catalytic ability of these Pd materials was compared with the commercial Pd on carbon material.
Fatal hypothermia in potbellied pigs. (1997)

Comment on: Rapid identification of porcine Serpulina species by colony blot assay using a genus-specific monoclonal antibody.
Testis-expressed protein TSGA10 - an auto-antigen in autoimmune polyendocrine syndrome type I (2007)

Autoimmune polyendocrine syndrome type 1 (APS1) is a rare monogenic autosomal recessive disorder. Autoimmune gonadal failure is often one of its features. The aim of this study was to identify targets of immune reactions associated with male autoimmune hypogonadism in APS1. Human testis cDNA expression library immunoscreening with APS1 patients' sera identified the protein testis-specific protein 10 (TSGA10), which is a testis-expressed protein with a key role in spermatogenesis. The corresponding serum autoantibodies were detected by Radioimmunoprecipitation assay in 3 of 40 male (7.5%) and 2 of 26 female (7.7%) APS1 patients but in none of either 32 patients with Addison's disease or 116 healthy controls (p = 0.0055). However, the TSGA10 antibodies in APS1 patients showed no correlation with testicular or ovarian failure or with autoimmune hypogonadism markers. Nevertheless, their presence in a proportion of patients with APS1 highlights the role of TSGA10 as a target of immune reactions in APS1.
High-Resolution Peptide Mapping Separations with MS-Friendly Mobile Phases and Charge-Surface-Modified C18 (2013)

Ionic analytes, such as peptides, can be challenging to separate by reverse-phase chromatography with optimal efficiency. They tend, for instance, to exhibit poor peak shapes, particularly when eluted with mobile phases preferred for electrospray ionization mass spectrometry. We demonstrate that a novel charged-surface C18 stationary phase alleviates some of the challenges associated with reverse-phase peptide separations. This column chemistry, known as CSH (charged-surface hybrid) C18, improves upon an already robust organosilica hybrid stationary phase, BEH (ethylene-bridged hybrid) C18. Based on separations of a nine-peptide standard, CSH C18 was found to exhibit improved loadability, greater peak capacities, and unique selectivity compared to BEH C18. Its performance was also seen to be significantly less dependent on TFA-ion pairing, making it ideal for MS applications where high sensitivity is desired. These performance advantages were evaluated through application to peptide mapping, wherein CSH C18 was found to aid the development of a high-resolution, high-sensitivity LC-UV-MS peptide mapping method for the therapeutic antibody, trastuzumab. From these results, the use of a C18 stationary phase with a charged surface, such as CSH C18, holds significant promise for facilitating challenging peptide analyses.
Understanding the Reactivity of a Thin Li1.5Al0.5Ge1.5(PO4)3 Solid‐State Electrolyte toward Metallic Lithium Anode (2020)

Abstract The thickness of solid‐state electrolytes (SSEs) significantly affects the energy density and safety performance of all‐solid‐state lithium batteries. However, a sufficient understanding of the reactivity toward lithium metal of ultrathin SSEs (&lt;100 µm) based on NASICON remains lacking. Herein, for the first time, a self‐standing and ultrathin (70 µm) NASICON‐type Li 1.5 Al 0.5 Ge 1.5 (PO 4 ) 3 (LAGP) electrolyte via a scalable solution process is developed, and X‐ray photoelectron spectroscopy reveals that changes in LAGP at the metastable Li–LAGP interface during battery operation is temperature dependent. Severe germanium reduction and decrease in LAGP particle size are detected at the Li–LAGP interface at elevated temperature. Oriented plating of lithium metal on its preferred (110) face occurs during in situ X‐ray diffraction cycling.
Correction: Macrophage Mitochondrial and Stress Response to Ingestion of Cryptococcus neoformans (2017)

Coelho, C., A. C. Oliveira Souza, L. da Silveira Derengowski, C. de Leon-Rodriguez, B. Wang, R. Leon-Rivera, A. Lorenzetti Bocca, T. Goncalves, and A. Casadevall. 2015. Macrophage mitochondrial and stress response to ingestion of Cryptococcus neoformans . J . Immunol . 194: [2345–2357][1].

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Insertions of transposon Tn5 into ribosomal protein PNA polymerase operons (1982)

The genetic organization and interrelationships between the two ribosomal protein transcription units (the L11 and L10 operons) from near 89 min on the Escherichia coli chromosome were studied by using insertional mutations generated by the kanamycin-resistant transposable element Tn5. The polar effects of Tn5 insertions on the expression of the L11, L1, L10, and L12 ribosomal protein genes and the beta RNA polymerase subunit gene were examined (i) by the level of beta-galactosidase activity generated from L10-lacZ and beta-lacZ gene fusions, (ii) by direct sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the proteins specified by plasmid ribosomal protein genes in UV-irradiated maxicells, and (iii) by urea-polyacrylamide gel electrophoresis of plasmid- and chromosome-specified L12 protein. The results confirmed the organization of these genes into two transcription units as follows: PL11, rplK (L11), rplA (L1), PL10, rplJ (L10), rplL (L12), rpoB (beta). . .; they also localized the position of the PL10 promoter within an 80-nucleotide region near the end of the L1 gene. The results also support the idea that the translational regulatory proteins for the L11 and L10 operons are L1 and L10, respectively, and that the expression of the L12 gene is closely linked to L10 gene expression.
A two-phase approach for stochastic optimization of complex business processes (2013)

Business process modeling is a well established methodology for analyzing and optimizing complex processes. To address critical challenges in ubiquitous black-box approaches, we develop a two-stage business process optimization framework. The first stage is based on an analytical approach that exploits structural properties of the underlying stochastic network and renders a near-optimal solution. Starting from this candidate solution, the second stage employs advanced simulation optimization to locally search for optimal business process solutions. Numerical experiments demonstrate the efficacy of our approach.
Block-Wise Resource Block-Level Distributed Transmission for Shared Data Channel in OFDMA Evolved UTRA Downlink (2009)

This paper proposes block-wise resource block (RB)-level distributed OFDMA transmission with ND-block division in order to obtain the frequency diversity effect even for low-rate traffic (here ND indicates the number of virtual RBs within one physical RB) in Evolved UTRA downlink. More specifically, we propose a constraint rule such that distributed transmission is multiplexed into a different physical RB from that of localized transmission in order to achieve the same resource assignment and independent decoding between the distributed and localized transmissions. Based on the proposed rule, a virtual RB for distributed transmission is segmented into ND blocks with the size of 1/ND of the original virtual RB. Then, the ND virtual blocks with the size of 1/ND are mapped together into each ND physical RB in a distributed manner, resulting in a large frequency diversity effect. Numerical calculations show that the block-wise RB-level distributed transmission can reduce the number of control signaling bits required for resource assignment compared to the subcarrier-level distributed transmission scheme, which provides the best performance. Moreover, a system-level simulation shows that the loss in the cell throughput employing the block-wise RB-level distributed transmission compared to that using the subcarrier-level transmission is only within 3-4% when the channel load is 0.5 and 1.0, i.e., the maximum loss is 3-4% at approximately 90% in the cumulative distribution function (CDF).
Area and energy efficient 802.11ad LDPC decoding processor (2015)

The design of multi‐Gbit/s low‐density parity‐check code (LDPC) decoders has become a hot topic in recent years to meet the growing demand of the transformation towards 4G. An area and energy efficient multi‐Gbit/s LDPC decoder engine with a fully paralleled layered architecture based on an application‐specific instruction set processor (ASIP) using Synopsys IP designer is presented. When the ASIP core is instantiated for 802.11ad, it achieved a throughput of up to 7 Gbit/s at three iterations with a latency of 95 ns, a record energy efficiency of 2.5 pJ/bit/iteration and an area efficiency of 54.5 Gbit/s/sq‐m in CMOS 28 nm technology for the 1/2 rate, showing it to be competitive against published ASIC solutions.
Renal Cell Cancer Invading the Inferior Vena Cava: Clinical Review and Anatomical Approach (1980)

Renal cell carcinoma invades the inferior vena cava in approximately 5 per cent of the patients. The only effective therapy for intravascular renal cell carcinoma is radical nephrectomy and complete removal of the tumor thrombus. To formulate a reasonable operative approach to intracaval renal cell carcinoma we have reviewed our experience with 6 cases as well as the experience of other investigators. In addition, we studied the collateral circulation of the renal veins as described by various anatomists, and to this information we have added our experience with inferior venacavography and with intraoperative and autopsy dissections. Herein we describe a new preoperative staging system for intravascular renal cell carcinoma. The operative approach to each stage is discussed in detail beneficial intraoperative maneuvers are described and illustrated.
Long-lasting desensitization of bladder afferents following intravesical resiniferatoxin and capsaicin in the rat (1995)

The present study was conducted to determine whether long-lasting desensitization of bladder afferents could be achieved using a single local application of the capsaicin (CAP)-like irritant resiniferatoxin (RTX), and to compare the effects of RTX and CAP on behavioral and histological endpoints. While rats were anesthetized, vehicle (VEH), RTX (10-100 nmol) or CAP (10-100 mumol) was instilled in the bladder (intravesical, i.ves.) via a cannula surgically implanted into the bladder dome. Beginning 1 week after treatment, once per week for 4 weeks, rats were tested behaviorally for desensitization to i.ves. RTX (10 nmol) using the abdominal lick test. Rats pretreated with low doses of RTX and CAP were partially desensitized at week 1; desensitization diminished over weeks 2-3. In contrast, rats pretreated with high doses of RTX or CAP were more completely desensitized at week 1, and desensitization did not diminish by week 4. Separate groups of rats tested 8 weeks after treatment showed substantial recovery. Rats pretreated with RTX but tested only with VEH for the first 3 weeks showed desensitization at week 4 approximately equivalent to that of RTX-treated rats tested with RTX every week. Sensitivity of corneal afferents to RTX (1.0 microgram/ml) at week 4 was not different between VEH- and RTX- or CAP-treated rats. Gross and histological examination of bladder tissue indicated that both RTX and CAP produced inflammation, which diminished in a dose- and time-dependent manner (1-8 weeks post-treatment).(ABSTRACT TRUNCATED AT 250 WORDS)
Development of a Two-Step Multiplex PCR Assay for Typing of Capsular Polysaccharide Synthesis Gene Clusters of Streptococcus suis (2014)

We developed a practical and easy two-step multiplex PCR assay to aid in serotyping of Streptococcus suis. The assay accurately typed almost all of the serotype reference strains and field isolates of various serotypes and also identified the genotypes of capsular polysaccharide synthesis gene clusters of some serologically nontypeable strains.