bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional Replacement of Nucleocapsid Flanking Regions by Heterologous Counterparts with Divergent Primary Sequences: Effects of Chimeric Nucleocapsid on the Retroviral Replication Cycle
Authors: Fu William , Hu Wei-Shau 
Published: December 2002

ABSTRACT

Nucleocapsid (NC) proteins in most retroviruses have a well-conserved Cys-His box(es) as well as more divergent flanking regions that are rich in basic residues. Mutations in the flanking regions can affect RNA packaging, virus assembly, and reverse transcription of the viral RNA. To gain a further understanding of the roles of NC flanking regions in the retroviral replication cycle, we generated and characterized chimeric
gag-pol
expression constructs derived from murine leukemia virus and spleen necrosis virus by replacing an NC flanking region from one virus with the counterpart from the other virus. We found that all four chimeras were able to generate virions, package viral RNA, and complete the viral replication cycle. Two chimeras had mild defects in virus assembly that correlated with a decrease in the isoelectric points of NCs, suggesting that the basic nature of NC is important in virus assembly. This finding indicates that, although the primary sequences of these flanking regions have little homology, the heterologous sequences are functional both as part of the Gag polyprotein and as processed NC protein.
Rice Grassy Stunt Tenuivirus
Nonstructural Protein p5 Interacts with Itself To Form Oligomeric Complexes In Vitro and In Vivo
Authors: Chomchan Pritsana , Li Shi-Fang , Shirako Yukio 
Published: December 2002

ABSTRACT

We investigated the interaction of
Rice grassy stunt tenuivirus
(RGSV) nonstructural protein p5, a protein of 22 kDa encoded on vRNA 5, with all 12 RGSV proteins by using a GAL4 transcription activator-based yeast two-hybrid system. The p5 protein interacted only with itself and not with any other viral protein; the interacting domains were localized within the N-terminal 96 amino acids of p5. The p5-p5 interaction was reproduced in an Sos recruitment-mediated yeast two-hybrid system as well in by far-Western blots. Native p5 protein extracted from RGSV-infected rice tissue was detected in a large complex with a molecular mass of approximately 260 kDa composed of 12 molecules of p5 or a p5 oligomer with an unidentified host factor(s).
Increased Virus Replication and Virulence after Serial Passage of Human Immunodeficiency Virus Type 2 in Baboons
Authors: Locher Christopher P. , Witt Stephanie A. , Herndier Brian G. , Abbey Nancy W. , Tenner-Racz Klara , Racz Paul , Kiviat Nancy B. , Murthy Krishna K. , Brasky Kathleen , Leland Michelle , Levy Jay A. 
Published: December 2002

ABSTRACTSimilar to human immunodeficiency virus type 1 (HIV-1) infection of humans, the natural history of HIV-2 infection in baboons (Papio cynocephalus) is a slow and chronic disease that generally takes several years before an AIDS-like condition develops. To shorten the amount of time to the development of disease, we performed five serial passages of HIV-2UC2in baboons by using blood and bone marrow samples during the acute phase of infection when viral loads were at high levels. After these serial passages, virus levels in plasma, peripheral blood mononuclear cells (PBMC) and lymphatic tissues in the acutely infected baboons were increased. Within 1 year of the HIV-2 infection, all of the inoculated baboons showed specific signs of AIDS-related disease progression within the lymphatic tissues, such as vascular proliferation and lymphoid depletion. The HIV-2UC2recovered after four serial passages showed increased kinetics of viral replication in baboon PBMC and cytopathicity. This study suggests that the HIV-2 isolate recovered after several serial passages in baboons will be useful in future studies of AIDS pathogenesis and vaccine development by using this animal model.
Evidence for Packaging of
rep-cap
Sequences into Adeno-Associated Virus (AAV) Type 2 Capsids in the Absence of Inverted Terminal Repeats: a Model for Generation of
rep
-Positive AAV Particles
Authors: Nony Pascale , Chadeuf Gilliane , Tessier Jacques , Moullier Philippe , Salvetti Anna 
Published: December 2002

ABSTRACT

We previously reported that a 350-bp region of the adeno-associated virus (AAV) type 2
rep
gene contains a
cis
-acting element responsible for the Rep-dependent replication of a transiently transfected
rep-cap
plasmid. In this study, we further report that replicated
rep-cap
sequences can be packaged into AAV capsids in the absence of the inverted terminal repeats.
Divergent Simian T-Cell Lymphotropic Virus Type 3 (STLV-3) in Wild-Caught
Papio hamadryas papio
from Senegal: Widespread Distribution of STLV-3 in Africa
Authors: Meertens Laurent , Gessain Antoine 
Published: December 2002

ABSTRACT

Among eight samples obtained from a French primatology research center, six adult guinea baboons (
Papio hamadryas papio
), caught in the wild in Senegal, had a peculiar human T-cell leukemia virus type 2 (HTLV-2)-like Western blot seroreactivity (p24
+
, GD21
+
, K55
+/−
). Partial sequence analyses of the
tax
genes (433 bp) indicated that these baboons were infected by a novel divergent simian T-cell lymphotropic virus (STLV). Analyses of the complete proviral sequence (8,892 bp) for one of these strains (STLV-3/PPA-F3) indicate that this STLV was highly divergent from the HTLV-1 (61.6% of nucleotide similarity), HTLV-2 (61.2%), or STLV-2 (60.6%) prototype. It was, however, much more closely related to the few other known STLV-3 strains, exhibiting 87 and 89% of nucleotide similarity with STLV-3/PHA-PH969 (formerly PTLV-L/PH969) and STLV-3/CTO-604, respectively. The STLV-3/PPA-F3 sequence possesses the major HTLV or STLV open reading frames corresponding to the structural, enzymatic, and regulatory proteins. However, its long terminal repeat comprises only two 21-bp repeats. In all phylogenetic analyses, STLV-3/PPA-F3 clustered together in a highly supported single clade with the other known strains of STLV-3, indicating an independent evolution from primate T-cell lymphotropic virus type 1 (PTLV-1) and PTLV-2. The finding of a new strain of STLV-3 in a West African monkey (Guinea baboon) greatly enlarges the geographical distribution and the host range of species infected by this PTLV type in the African continent. The recent discovery of several different STLV-3 strains in many different African monkey species, often in contact with humans, strongly suggests potential interspecies transmission events, as it was described for STLV-1, between nonhuman primates but also to humans.
Poliovirus-Induced Apoptosis Is Reduced in Cells Expressing a Mutant CD155 Selected during Persistent Poliovirus Infection in Neuroblastoma Cells
Authors: Gosselin Anne-Sophie , Simonin Yannick , Guivel-Benhassine Florence , Rincheval Vincent , Vayssière Jean-Luc , Mignotte Bernard , Colbère-Garapin Florence , Couderc Thérèse , Blondel Bruno 
Published: December 2002

ABSTRACT

Poliovirus (PV) can establish persistent infections in human neuroblastoma IMR-32 cells. We previously showed that during persistent infection, specific mutations were selected in the first extracellular domain of the PV receptor (CD155) of these cells (N. Pavio, T. Couderc, S. Girard, J. Y. Sgro, B. Blondel, and F. Colbère-Garapin, Virology
274:
331-342, 2000). These mutations included the Ala 67 → Thr substitution, corresponding to a previously described allelic form of the PV receptor. The mutated CD155
Thr67
and the nonmutated IMR-32 CD155 (CD155
IMR
) were expressed independently in murine LM cells lacking the CD155 gene. Following infection of the cells with PV, we analyzed the death of cells expressing these two forms of CD155. Levels of DNA fragmentation, caspase activity, and cytochrome
c
release were lower in LM-CD155
Thr67
cells than in LM-CD155
IMR
cells. Thus, the level of apoptosis was lower in cells expressing mutated CD155 selected during persistent PV infection in IMR-32 than in cells expressing the wild-type receptor.
Overcoming Immunity to a Viral Vaccine by DNA Priming before Vector Boosting
Authors: Yang Zhi-yong , Wyatt Linda S. , Kong Wing-pui , Moodie Zoe , Moss Bernard , Nabel Gary J. 
Published: December 2002

ABSTRACT
Replication-defective adenovirus (ADV) and poxvirus vectors have shown potential as vaccines for pathogens such as Ebola or human immunodeficiency virus in nonhuman primates, but prior immunity to the viral vector in humans may limit their clinical efficacy. To overcome this limitation, the effect of prior viral exposure on immune responses to Ebola virus glycoprotein (GP), shown previously to protect against lethal hemorrhagic fever in animals, was studied. Prior exposure to ADV substantially reduced the cellular and humoral immune responses to GP expressed by ADV, while exposure to vaccinia inhibited vaccine-induced cellular but not humoral responses to GP expressed by vaccinia. This inhibition was largely overcome by priming with a DNA expression vector before boosting with the viral vector. Though heterologous viral vectors for priming and boosting can also overcome this effect, the paucity of such clinical viral vectors may limit their use. In summary, it is possible to counteract prior viral immunity by priming with a nonviral, DNA vaccine.
Genetic Interaction between Distinct Dobrava Hantavirus Subtypes in
Apodemus agrarius
and
A. flavicollis
in Nature
Authors: Klempa Boris , Schmidt Heiko A. , Ulrich Rainer , Kaluz Stefan , Labuda Milan , Meisel Helga , Hjelle Brian , Krüger Detlev H. 
Published: December 2002

ABSTRACT

Dobrava virus (DOBV) occurs in two different rodent species,
Apodemus flavicollis
(DOBV-Af) and
A. agrarius
(DOBV-Aa). We sequenced the S and M genomic segments from sympatric DOBV-Af and DOBV-Aa strains which fell into two distinct genetic lineages. Molecular phylogenetic analyses gave evidence for genetic reassortment between S and M segments of DOBV-Af and DOBV-Aa and indicated homologous recombination events in DOBV evolution. DOBV-Af and DOBV-Aa are distinct but also subject to genetic exchanges that affect their evolutionary trajectories.
Sequences Downstream of the 5′ Splice Donor Site Are Required for both Packaging and Dimerization of Human Immunodeficiency Virus Type 1 RNA
Authors: Russell Rodney S. , Hu Jing , Bériault Véronique , Mouland Andrew J. , Kleiman Lawrence , Wainberg Mark A. , Liang Chen 
Published: December 2002

ABSTRACT
Two copies of human immunodeficiency virus type 1 RNA are incorporated into each virus particle and are further converted to a stable dimer as the virus particle matures. Several RNA segments that flank the 5′ splice donor site at nucleotide (nt) 289 have been shown to act as packaging signals. Among these, RNA stem-loop 1 (SL1) (nt 243 to 277) can trigger RNA dimerization through a “kissing-loop” mechanism and thus is termed the dimerization initiation site. However, it is unknown whether other packaging signals are also needed for dimerization. To pursue this subject, we mutated stem-loop 3 (SL3) (nt 312 to 325), a GA-rich region (nt 325 to 336), and two G-rich repeats (nt 363 to 367 and nt 405 to 409) in proviral DNA and assessed the effects on RNA dimerization by performing native Northern blot analyses. Our results show that the structure but not the specific RNA sequence of SL3 is needed not only for efficient viral RNA packaging but also for dimerization. Mutations of the GA-rich sequence severely diminished viral RNA dimerization as well as packaging; the combination of mutations in both SL3 and the GA-rich region led to further decreases, implying independent roles for each of these two RNA motifs. Compensation studies further demonstrated that the RNA-packaging and dimerization activity of the GA-rich sequence may not depend on a putative interaction between this region and a CU repeat sequence at nt 227 to 233. In contrast, substitutions in the two G-rich sequences did not cause any diminution of viral RNA packaging or dimerization. We conclude that both the SL3 motif and GA-rich RNA sequences, located downstream of the 5′ splice donor site, are required for efficient RNA packaging and dimerization.
Heterodimerization of the Two Major Envelope Proteins Is Essential for Arterivirus Infectivity
Authors: Snijder Eric J. , Dobbe Jessika C. , Spaan Willy J. M. 
Published: December 2002

ABSTRACT

The two major envelope proteins of arteriviruses, the membrane protein (M) and the major glycoprotein (GP
5
), associate into a disulfide-linked heterodimer that is incorporated into the virion and has been assumed to be a prerequisite for virus assembly. Using an equine arteritis virus (EAV) infectious cDNA clone, we have analyzed the requirement for GP
5
-M heterodimerization and have identified the Cys residues involved in the formation of the GP
5
-M disulfide bond. The single Cys residue (Cys-8) in the M ectodomain was crucial for heterodimerization and virus infectivity. Mutagenesis of any of the five Cys residues in the GP
5
ectodomain or removal of the single GP
5
N-glycosylation site also rendered the full-length clone noninfectious. However, an analysis of revertants yielded an exceptional pseudorevertant in which residues 52 to 79 of the GP
5
ectodomain had been deleted and the original Cys-80→Ser mutation had been maintained. Consequently, this revertant lacked the GP
5
N-glycosyation site (Asn-56) and retained only a single cysteine residue (Cys-34). By using this GP
5
deletion, we confirmed that Cys-34 of GP
5
and Cys-8 of M are essential for GP
5
-M heterodimerization, a key event in the assembly of the EAV envelope.
OPERATING SYSTEMS TECHNIQUES FOR PARALLEL COMPUTATION IN INTELLIGENT MEMORY
Authors: OSKIN MARK , KEEN DIANA , HENSLEY JUSTIN , LITA LUCIAN-VLAD , CHONG FREDERIC T. 
Published: December 2002

Advances in DRAM density have led to several proposals to perform computation in memory [1] [2] [3]. Active Pages is a page-based model of intelligent memory that can exploit large amounts of parallel computation in data-intensive applications. With a simple VLIW processor embedded near each page on DRAM, Active Page memory systems achieve up to 1000X speedups over conventional memory systems [4]. Active Pages are specifically designed to support virtualized hardware resources. In this study, we examine operating system techniques that allow Active Page memories to share, or multiplex, embedded VLIW processors across multiple physical Active Pages. We explore the trade-off between individual page-processor performance and page-level multiplexing. We find that hardware costs of computational logic can be reduced from 31% of DRAM chip area to 12%, through multiplexing, without significant loss in performance. Furthermore, manufacturing defects that disable up to 50% of the page processors can be tolerated through efficient resource allocation and associative multiplexing.
Isocupressic Acid Blocks Progesterone Production from Bovine Luteal Cells
Authors: Wu L. S. , Chen Joyce C. , Sheu S. Y. , Huang C. C. , Kuo Y. H. , Chiu C. H. , Lian W. X. , Yang C. J. , Kaphle K. , Lin J. H. 
Published: December 2002

The needles of ponderosa pine (Pinus ponderosa Laws.) were reported to induce abortions when fed to late-term pregnant beef cows in North America. An in vivo study of pregnant cows suggested that isocupressic acid (IA) was the main abortifacient isolated from needles and bark of the pine. However, the mechanism of abortifacient activity of IA is not clear yet. In a pregnant cow, the corpus luteum of the ovary helps the maintenance of pregnancy by its progesterone production. This study involved the IA extracted from the root of the Taiwan cypress (Juniperus formosana) and used a frozen-thawed bovine luteal cell culture system to investigate the action of IA on progesterone production. Thawed bovine luteal cells (1 × 105 cells/ml/well) in M199 medium were cultured in 24-well culture plates at 37°C in a 5% CO 2 incubator. Ten ml of tested drugs, IA at 1 to 1000 ng/ml and/or ovine luteinizing hormone (oLH) at 1 to 100 ng/μl or 8-bromo-cyclic adenosine monophosphate (8-Br-cAMP) with 0.1-10 mM, were added into each well. After 4 hours of incubation, the media were harvested and assayed for progesterone by an enzyme immunoassay. Progesterone production from cells was the indicator used to evaluate the action of IA. All tested doses of IA significantly inhibited progesterone production in both basal and oLH stimulating conditions. Also those dosages inhibited cyclic adenosine-3', 5'- monophosphate (cAMP) stimulation, suggesting a post-cAMP mechanism is involved in the IA action. We concluded that IA can induce pregnant cows to abort partly through blocking luteal function and may be identified as a new abortifacient chemical.
GOING BEYOND EXPLICIT KNOWLEDGE FOR IMPROVED SEMANTIC BASED INFORMATION RETRIEVAL
Authors: MIHALCEA RADA F. 
Published: December 2002

This paper proposes a novel model that incorporates word semantics into information retrieval, enabling a whole new range of semantic based retrieval applications. Concepts can be sought instead of simple words, and the retrieval of words that are semantically related to the input keywords is also possible. A novel encoding scheme applied to words creates the groundwork for this model and enables the application of complex semantic operators. One of the most powerful operators introduced by the model is the semantic wildcard, able to fulfill information requests expressed along general-specific lines. For instance, a search for animal# will match any concept that is of type animal, going beyond the explicit knowledge stated in texts. Additionally, a new lexical locality operator is introduced, making possible the retrieval of paragraphs rather than entire documents. Both semantic indexing and paragraph indexing paradigms proposed in the model have been implemented in a system that was tested on questions run against an index of 130,000 documents. A significant improvement was observed over classic keyword based retrieval systems, in terms of precision, recall and success rate.
Association Between the Medicare Advantage Quartile Adjustment System and Plan Behavior and Enrollment
Authors: Murray Roslyn C. , Meyers David J. , Fuse Brown Erin C , Williams Travis C. , Ryan Andrew M. 
Published: January 2024

ImportanceMedicare Advantage (MA) has grown in popularity, but critics believe that insurers are overpaid, partially due to the quartile adjustment system that determines plan benchmarks. However, elimination of the quartile adjustments may be associated with less generous benefits and fewer plan offerings, which could slow MA enrollment growth.ObjectiveTo examine whether the quartile adjustment system is associated with differences in county-level benefits, insurer offerings, and MA enrollment.Design, Setting, and ParticipantsThe quartile adjustments create discontinuous jumps in county-level base payments based on historical traditional Medicare spending. Data from January 2017 to December 2021 and a regression discontinuity design were used to examine changes in insurer behavior and MA enrollment between quartiles. The analytic sample included 1557 county observations.Main Outcomes and MeasuresStudy outcomes included monthly premiums, the share of plans charging premiums, primary care copayments, the share of plans using rebates to reduce Part B premiums, supplemental benefits, plan and contract availability, and MA enrollment.ResultsDiscontinuities were found in the quartile adjustments and benchmarks. A 1–percentage point (pp) increase in the quartile adjustment was associated with a $6.36 increase in monthly benchmarks (95% CI, 5.10-7.62), a $0.51 decrease in monthly premiums (95% CI, −0.96 to −0.07), and a 0.68 pp decrease in the share of plans charging premiums (95% CI, −1.25 to −0.10). Significant changes were not found in primary care copayments (-$0.04; 95% CI, −0.17 to 0.09), the share of plans using rebates to reduce Part B premiums (−0.17 pp; 95% CI, −0.34 to 0.01), supplemental benefits (eg, preventive dental coverage; 0.17 pp; 95% CI, −0.25 to 0.0), the number of plans (1.06; 95% CI, −3.44 to 5.57) or contracts (0.31; 95% CI, −0.18 to 0.81), or the MA enrollment rate (0.16 pp; 95% CI, −0.61 to 0.94).Conclusions and RelevanceThe study results suggest that MA plans are not very sensitive to modest changes in payment rates. Modifications to the quartile adjustment system may generate savings without substantially affecting MA beneficiaries.
Adverse Safety Events in Emergency Medical Services Care of Children With Out-of-Hospital Cardiac Arrest
Authors: Eriksson Carl O. , Bahr Nathan , Meckler Garth , Hansen Matthew , Walker-Stevenson Grace , Idris Ahamed , Aufderheide Tom P. , Daya Mohamud R. , Fink Ericka L. , Jui Jonathan , Luetje Maureen , Martin-Gill Christian , Mcgaughey Steven , Pelletier Jon , Thomas Danny , Guise Jeanne-Marie ,   Child Safety Initiative–Emergency Medical Services for Children, Harrod Tabria , Schoonover Amanda , Ivankovic Jon 
Published: January 2024

ImportanceSurvival for children with out-of-hospital cardiac arrest (OHCA) remains poor despite improvements in adult OHCA survival.ObjectiveTo characterize the frequency of and factors associated with adverse safety events (ASEs) in pediatric OHCA.Design, Setting, and ParticipantsThis population-based retrospective cohort study examined patient care reports from 51 emergency medical services (EMS) agencies in California, Georgia, Oregon, Pennsylvania, Texas, and Wisconsin for children younger than 18 years with an OHCA in which resuscitation was attempted by EMS personnel between 2013 and 2019. Medical record review was conducted from January 2019 to April 2022 and data analysis from October 2022 to February 2023.Main Outcomes and MeasureSevere ASEs during the patient encounter (eg, failure to give an indicated medication, 10-fold medication overdose).ResultsA total of 1019 encounters of EMS-treated pediatric OHCA were evaluated; 465 patients (46%) were younger than 12 months. At least 1 severe ASE occurred in 610 patients (60%), and 310 patients (30%) had 2 or more. Neonates had the highest frequency of ASEs. The most common severe ASEs involved epinephrine administration (332 [30%]), vascular access (212 [19%]), and ventilation (160 [14%]). In multivariable logistic regression, the only factor associated with severe ASEs was young age. Neonates with birth-related and non–birth-related OHCA had greater odds of a severe ASE compared with adolescents (birth-related: odds ratio [OR], 7.0; 95% CI, 3.1-16.1; non–birth-related: OR, 3.4; 95% CI, 1.2-9.6).Conclusions and RelevanceIn this large geographically diverse cohort of children with EMS-treated OHCA, 60% of all patients experienced at least 1 severe ASE. The odds of a severe ASE were higher for neonates than adolescents and even higher when the cardiac arrest was birth related. Given the national increase in out-of-hospital births and ongoing poor outcomes of OHCA in young children, these findings represent an urgent call to action to improve care delivery and training for this population.