gebhart/patrepeval huggingface dataset:
Neurofilament and neural cell adhesion molecule immunocytochemistry of Huntington's disease striatum (1992)

We examined normal and Huntington's disease (HD) human striatum with specific monoclonal antibodies to nonphosphorylated (SMI 32) and phosphorylated (SMI 31) neurofilament and neural cell adhesion molecule (NCAM). SMI 32 identifies medium-sized neuronal perikarya and dendrites in normal striatum. Axons are not immunoreactive. In high-grade HD striatum (grades 3 and 4) SMI 32 neurons are morphologically abnormal and significantly depleted. Dendritic arbors are intensely immunoreactive, tortuous, and fragmented, especially in the subependymal zone. Proliferative SMI 32-positive sprout-like structures and axon-like processes are seen. SMI 31 normally stains a fine meshwork of axon-like processes that become intensely immunoreactive, condensed, convoluted, and fragmented in HD. NCAM staining is minimal in normal striatum, but, in HD striatum, many dot- and thread-like structures are found, especially in the subependymal region. The abnormalities revealed by SMI 31, SMI 32, and NCAM suggest that neurofilament phosphorylation is altered and growth related proteins are reexpressed in HD. Dephosphorylation and destabilization of the cytoskeleton may contribute to neuronal injury and death in HD.
A New Transformation-Deficient Mutant of Haemophilus influenzae Rd with Normal DNA Uptake (1998)

Haemophilus influenzae Rd is a gram-negative natural transformer. A mutant strain, RJ248, that has normal DNA uptake and translocation but whose transformation frequency is 300 times lower than that of wild-type H. influenzae and whose phage recombination is 8 times lower was isolated. The affected gene, comM, is induced during competence development in wild-type H. influenzae but not in RJ248.
Interleukin 10 modulation of pathogenic Th17 cells during fatal alphavirus encephalomyelitis (2014)

Mosquito-borne alphaviruses are important causes of epidemic encephalomyelitis. Neuronal cell death during fatal alphavirus encephalomyelitis is immune-mediated; however, the types of cells involved and their regulation have not been determined. We show that the virus-induced inflammatory response was accompanied by production of the regulatory cytokine IL-10, and in the absence of IL-10, paralytic disease occurred earlier and mice died faster. To determine the reason for accelerated disease in the absence of IL-10, immune responses in the CNS of IL-10(-/-) and wild-type (WT) mice were compared. There were no differences in the amounts of brain inflammation or peak virus replication; however, IL-10(-/-) animals had accelerated and increased infiltration of CD4(+)IL-17A(+) and CD4(+)IL-17A(+)IFNγ(+) cells compared with WT animals. Th17 cells infiltrating the brain demonstrated a pathogenic phenotype with the expression of the transcription factor, Tbet, and the production of granzyme B, IL-22, and GM-CSF, with greater production of GM-CSF in IL-10(-/-) mice. Therefore, in fatal alphavirus encephalomyelitis, pathogenic Th17 cells enter the CNS at the onset of neurologic disease and, in the absence of IL-10, appear earlier, develop into Th1/Th17 cells more often, and have greater production of GM-CSF. This study demonstrates a role for pathogenic Th17 cells in fatal viral encephalitis.
Use of rapid diagnostic tests and choice of antibiotics in respiratory tract infections in primary healthcare—A 6-y follow-up study (2009)

The aim of this retrospective study of electronic patient records in primary health care in Kalmar County, Sweden, was to describe consultations for respiratory tract infections (RTIs) in relation to age, choice of antibiotics and the use of rapid diagnostic tests. During the period 1999-2005, 240,445 visits for RTI were recorded. Children aged <2 y and especially those aged 2-16 y with acute otitis media (AOM), showed decreasing consultations between 2000 and 2005. The consultations for sore throat declined during the study period in all age groups and in 65% of these, antibiotics were prescribed, primarily penicillin V (82%). In sore throat, a positive Strep-A test result was followed by antibiotic prescription in about 92% of cases; when negative, the antibiotic prescription rate was 40%. C-reactive protein (CRP) was analyzed in 36% of all consultations for RTI. In common cold and acute bronchitis, the prescription rates of antibiotics rose with rising CRP. The results show that near-patient tests were used extensively, but often not in accordance with the guidelines. Antibiotic use decreased mainly as a consequence of declined visiting frequencies. This indicates that the new guidelines for AOM and sore throat may have influenced patient consultation habits more than physician prescribing habits.
Central neural mechanisms mediating human visceral hypersensitivity (2001)

Although visceral hypersensitivity is thought to be important in generating symptoms in functional gastrointestinal disorders, the neural mechanisms involved are poorly understood. We recently showed that central sensitization (hyperexcitability of spinal cord sensory neurones) may play an important role. In this study, we demonstrate that after a 30-min infusion of 0.15 M HCl acid into the healthy human distal esophagus, we see a reduction in the pain threshold to electrical stimulation of the non-acid-exposed proximal esophagus (9.6 +/- 2.4 mA) and a concurrent reduction in the latency of the N1 and P2 components of the esophageal evoked potentials (EEP) from this region (10.4 +/- 2.3 and 15.8 +/- 5.3 ms, respectively). This reduced EEP latency indicates a central increase in afferent pathway velocity and therefore suggests that hyperexcitability within the central visceral pain pathway contributes to the hypersensitivity within the proximal, non-acid-exposed esophagus (secondary hyperalgesia/allodynia). These findings provide the first electrophysiological evidence that central sensitization contributes to human visceral hypersensitivity.
Eight-bit CPU with Nonvolatile Registers Capable of Holding Data for 40 Days at 85°C Using Crystalline In-Ga-Zn Oxide Thin Film Transistors (2012)

2012 International Conference on Solid State Devices and Materials,Eight-bit CPU with Nonvolatile Registers Capable of Holding Data for 40 Days at 85°C Using Crystalline In-Ga-Zn Oxide Thin Film Transistors
Personalized Cancer Therapy With Selective Kinase Inhibitors: An Emerging Paradigm in Medical Oncology (2009)

Selective kinase inhibitors have emerged as an important class of anticancer agents, with demonstrated clinical efficacy and generally favorable toxicity profiles in several common disease settings where conventional treatments have previously provided only modest benefit. Consequently, a substantial effort is now underway to identify additional therapeutically relevant kinase targets and to develop and test inhibitors of those proteins in a variety of human malignancies. However, it has also become clear that the clinical benefit associated with these agents is typically limited to a subset of treated patients, who in many cases are defined by a specific genomic lesion within their tumor cells--frequently, an activating mutation within the gene encoding the target kinase. This discovery has prompted efforts to stratify patients before treatment with kinase inhibitors based on specific genomic biomarkers, with the goal of optimizing clinical outcomes through the effective personalization of treatment (ie, matching the right patients with the right therapies). With recent advances in our understanding of the relationship between tumor genotypes and cancer cell sensitivity to kinase inhibition, together with improved technologies for rapidly genotyping tumor biopsies for relevant lesions, the implementation of personalized cancer care with this exciting new class of inhibitors is now becoming a reality. In this review, we summarize recent developments in this area, and we highlight some of the logistical challenges posed by this emerging paradigm in medical oncology.
Probing the human receptor for C5a anaphylatoxin with site-directed antibodies. Identification of a potential ligand binding site on the NH2-terminal domain. (1993)

Molecular cloning has revealed the DNA sequence of the human receptor for the C5a anaphylatoxin (C5aR). In this study, mAb and polyclonal antibodies with specificities for deduced hydrophilic sequences of the receptor protein were employed to determine the expression and the topography of C5aR on PBL. Evidence was obtained that an antigenically homogenous receptor exists on human neutrophils, eosinophils, and monocytes that binds C5a and C5a(desArg). The assignment of epitopes to extra- or intracellular receptor domains as determined by FACS analysis of intact or permeabilized cells confirmed the general topography of the C5aR that had been predicted by hydropathy analysis. Competitive binding studies were performed to examine whether extracellular receptor domains participate in ligand binding. The occupation of the receptor by C5a inhibited only the binding of antibodies that were specific for the receptor's aminoterminal domain (C5aR-EX1). The anti-EX1 mAb S5/1 effectively antagonized C5a/C5a(desArg) biological activity. A heptameric peptide (D15DKDTLD21) was identified as the smallest receptor fragment that was recognized by the mAb S5/1 or by polyclonal rabbit anti-EX1 lg. These results imply that an amino acid sequence rich in aspartate within the receptor aminoterminus represents both an immunodominant epitope and a ligand binding site on the C5aR.
Protein PAB, a mosaic albumin-binding bacterial protein representing the first contemporary example of module shuffling. (1994)

Some strains of the anaerobic human commensal and pathogen Peptostreptococcus magnus bind human serum albumin (HSA), whereas other strains of this species express protein L, an immunoglobulin light chain-binding surface protein. A novel HSA-binding protein called protein PAB was purified in one step from the culture supernatant of an HSA-binding strain of P. magnus by affinity chromatography on HSA-Sepharose. The apparent size of the molecular was 47 kDa on SDS-polyacrylamide gel electrophoresis. Amino acid sequence analysis of protein PAB demonstrated that the 4 NH2-terminal residues were identical to the corresponding sequence in protein L. In a polymerase chain reaction, oligonucleotides based on extragenic 5'- and 3'-end sequences of the protein L gene generated a product of the expected size: 1.3 kilobase pairs. A recombinant protein with retained albumin binding capacity was expressed in Escherichia coli, and the nucleotide sequence of the protein PAB gene was determined. The structural gene is 1161 nucleotides long, corresponding to a preprotein of 387 amino acids and a molecular mass of 43,043 Da. Unlike most other Gram-positive bacterial surface proteins described, protein PAB contains no internal homologies. However, substantial homologies were found to both proteins L and G (the IgG- and HSA-binding surface protein of group C and G streptococci). The derived amino acid sequence of the 135-base pair-long region homologous to protein G corresponds to the HSA-binding domain of that protein, and in protein PAB, this region is inserted between sequences showing extensive homology to COOH-terminal regions of peptostreptococcal protein L. This mosaic organization of protein PAB demonstrates that the molecule is a product of intergenic interspecies recombination of a functional domain into a common framework for peptostreptococcal surface proteins. Such an interspecies exchange of a functional protein module has previously not been described in prokaryotic cells.
Toxic Potential of Materials at the Nanolevel (2006)

Nanomaterials are engineered structures with at least one dimension of 100 nanometers or less. These materials are increasingly being used for commercial purposes such as fillers, opacifiers, catalysts, semiconductors, cosmetics, microelectronics, and drug carriers. Materials in this size range may approach the length scale at which some specific physical or chemical interactions with their environment can occur. As a result, their properties differ substantially from those bulk materials of the same composition, allowing them to perform exceptional feats of conductivity, reactivity, and optical sensitivity. Possible undesirable results of these capabilities are harmful interactions with biological systems and the environment, with the potential to generate toxicity. The establishment of principles and test procedures to ensure safe manufacture and use of nanomaterials in the marketplace is urgently required and achievable.
GENE DELIVERY WITHOUT VIRUSES (2001)

RETURN TO ISSUEPREVNewsNEXTGENE DELIVERY WITHOUT VIRUSESNonviral methods represent only a fraction of the gene delivery field, but they are catching up with viral vectorsCELIA M. HENRYView Author Information C&EN WASHINGTONCite this: Chem. Eng. News 2001, 79, 48, 35–41Publication Date (Print):November 26, 2001Publication History Published online13 November 2010Published inissue 26 November 2001https://pubs.acs.org/doi/10.1021/cen-v079n048.p035https://doi.org/10.1021/cen-v079n048.p035newsACS PublicationsCopyright © 2001 American Chemical SocietyArticle Views16Altmetric-Citations19LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access options SUBJECTS:Gene delivery,Gene therapy,Genetics,Viruses Get e-Alerts
Targeted gene delivery to Kaposi's sarcoma cells via the fibroblast growth factor receptor. (1997)

Kaposi's sarcoma (KS) is a major AIDS-related malignancy associated with significant morbidity and mortality. Current chemotherapeutic regimens are associated with a dismal prognosis. In an effort to develop a new approach to KS treatment, we devised a gene therapy-based adenovirus retargeting schema that redirects the adenovirus to fibroblast growth factor receptors endogenously present on the cell surface of KS cells. By using a bifunctional conjugate consisting of a blocking antiadenoviral knob Fab linked to basic fibroblast growth factor, FGF2, the gene transduction of KS cells was enhanced 7.7-44 fold; recombinant adenoviruses encoding either the firefly luciferase reporter gene, or the herpes simplex thymidine kinase gene, demonstrated quantitative enhancement of expression in the KS cell lines. In this regard, two KS cell lines that were previously refractory to native adenovirus transduction could be successfully transduced by the addition of the conjugate. This study thus addresses the utility of adenoviral retargeting to the FGF receptor in KS cells that are ordinarily transduction refractory to standardized approaches and allows practical development of gene therapy approaches for the treatment of human KS.
The use of circular dichroism to study conformational changes induced in Sendai virus envelope glycoproteins. A correlation with the viral fusogenic activity. (1986)

Fusion of Sendai virus envelopes with erythrocyte membranes or with phosphatidylcholine/cholesterol liposomes requires the presence of the two viral glycoproteins, namely the hemagglutinin/neuraminidase (HN) and the fusion (F) polypeptides. Membrane vesicles bearing only the HN or the F glycoprotein (HN or F vesicles) or a mixture of both do not possess fusogenic activity. These results clearly show that in order to be fusogenic, the two viral envelope glycoproteins must be present within the same membrane, thus indicating their mutual interaction. Circular dichroism studies revealed that the conformation of the viral glycoproteins in reconstituted viral envelopes or in HN-F vesicles (vesicles formed by co-reconstitution of the HN and F glycoproteins) is different from that of the conformation of these glycoproteins in either HN or F vesicles or in a mixture of both. It has been observed that the mean residue ellipticity as measured at 222 nm (theta 222) of the viral glycoproteins in reconstituted Sendai virus envelopes (RSVE) is lower by about 75% than the value observed for these glycoproteins in isolated HN or F vesicles. Treatment of RSVE or of HN-F vesicles with inhibitors of the viral fusogenic activity such as phenylmethylsulfonyl fluoride, proteolytic enzymes, or incubation at 70 degrees C caused a substantial conformational change in the viral glycoproteins. The theta 222 of unfusogenic RSVE or unfusogenic HN-F vesicles is very close to that observed for a mixture of HN and F vesicles. It is proposed here that in order to be fusogenic, the viral envelope glycoproteins must possess a certain conformation which exists only when they are present within the same membrane.
Azacitidine Prolongs Survival and Time to AML Transformation in High-Risk Myelodysplastic Syndrome (MDS) Patients ≥ 65 Years of Age. (2005)

Abstract The prognosis for patients with refractory anemia with excess blasts (RAEB) or RAEB in transformation (RAEB-T) ≥ 65 years of age has been poor. These high-risk patients are often not eligible for intensive induction/transplantation regimens or combination chemotherapies, leaving few treatment options besides supportive or palliative care. In the publication of the CALGB trial by Silverman et al (JCO2002;20:2429), no age- and/or risk- related subgroup analyses for azacitidine (Vidaza®) were presented. To assess the treatment effect of azacitidine versus supportive care on survival and time to AML transformation in a homogeneous sample of high-risk patients with MDS, we performed a subgroup analysis on the 191 patients included in the CALGB trial. All patients with a baseline diagnosis of RAEB or RAEB-T who were ≥ 65 years of age were included in the comparative analysis, using intent-to-treat (ITT) principles based on randomization to azacitidine or supportive care. Efficacy was analyzed using three survival endpoints: overall survival, time to death or AML transformation, and time to AML transformation. In all, 31 azacitidine patients and 37 supportive care patients met the criteria for this high-risk subgroup analysis. No significant differences in demographics or disease characteristics between the two groups were observed. For all three survival analyses, a statistically significant difference was observed for patients in the azacitidine group compared with those in the supportive care group. (Table) Median time to transformation to AML, in particular, was prolonged for 24 months in azacitidine patients compared with patients in the supportive care group. A sensitivity analysis of the overall survival results was conducted by performing 10 additional subgroup analyses based on ages ≥ 60 through ≥ 70 years in increments of one year with all overall survival results remaining significant (p &amp;lt; 0.05, except for 2 subgroup analyses based on ages ≥ 60 and ≥ 66 where both p-values were 0.051). The sensitivity results demonstrated robust patient benefit in the subgroup ≥ 65 years of age. The most common adverse event observed with azacitidine was myelosuppression, which decreased in frequency as therapy continued. Azacitidine provided clear treatment effect and patient benefit to this difficult-to-treat, high-risk group of RAEB and RAEB-T patients ≥ 65 years of age by significantly prolonging overall survival and time to AML transformation. Time of Even Analysis
Structural basis for nicotinamide cleavage and ADP-ribose transfer by NAD + -dependent Sir2 histone/protein deacetylases (2004)

Sir2 enzymes are broadly conserved from bacteria to humans and have been implicated to play roles in gene silencing, DNA repair, genome stability, longevity, metabolism, and cell physiology. These enzymes bind NAD(+) and acetyllysine within protein targets and generate lysine, 2'-O-acetyl-ADP-ribose, and nicotinamide products. To provide structural insights into the chemistry catalyzed by Sir2 proteins we report the high-resolution ternary structure of yeast Hst2 (homologue of Sir two 2) with an acetyllysine histone H4 peptide and a nonhydrolyzable NAD(+) analogue, carba-NAD(+), as well as an analogous ternary complex with a reaction intermediate analog formed immediately after nicotinamide hydrolysis, ADP-ribose. The ternary complex with carba-NAD(+) reveals that the nicotinamide group makes stabilizing interactions within a binding pocket harboring conserved Sir2 residues. Moreover, an asparagine residue, N116, strictly conserved within Sir2 proteins and shown to be essential for nicotinamide exchange, is in position to stabilize the oxocarbenium intermediate that has been proposed to proceed the hydrolysis of nicotinamide. A comparison of this structure with the ADP-ribose ternary complex and a previously reported ternary complex with the 2'-O-acetyl-ADP-ribose reaction product reveals that the ribose ring of the cofactor and the highly conserved beta1-alpha2 loop of the protein undergo significant structural rearrangements to facilitate the ordered NAD(+) reactions of nicotinamide cleavage and ADP-ribose transfer to acetate. Together, these studies provide insights into the chemistry of NAD(+) cleavage and acetylation by Sir2 proteins and have implications for the design of Sir2-specific regulatory molecules.
Investigation of attenuation increase at lower-side frequency bands for highly-integrated SAW modules (2006)

High attenuation characteristics are required at transmitter frequency bands, i.e. lower-side frequency ranges, for receiver surface acoustic ware (SAW) filters especially used in CDMA systems, where transmission and reception are performed simultaneously. Demonstrated is the possibility of new chip-level improvement for attenuation characteristics at these bands without external inductors and capacitors.
WEED SCIENCE Cotton Tolerance to Fomesafen Applied Preemergence (2012)

Field studies were conducted in Georgia, North Carolina, South Carolina, Tennessee, and Virginia during 2006 to investigate tolerance of cotton to fomesafen applied preemergence (PRE). Fomesafen at seven rates, and two standard herbicides, pyrithiobac and fluometuron, were applied PRE to cotton in a weed-free environment. Cotton tolerance to fomesafen was directly related to rainfall that occurred from planting through cotton emergence. No injury was detected in South Carolina or Tennessee, but heavy rainfalls prior to cotton emergence in Georgia led to 3 to 9% early season visible stunting by fomesafen at 140 to 420 g a.i. ha -1 and 11 to 15% stunting by fomesafen at 560 and 840 g ha -1 . In North Carolina and Virginia, rainfall during cotton emergence led to early season cotton necrosis ranging from 4 to 16% with fomesafen at 140 to 350 g ha -1 and 12 to 45% by fomesafen at 420 to 840 g ha -1 . Early season injury by fomesafen at 280 g ha -1 (recommended use rate) was equal to or less than pyrithiobac or fluometuron at 4 of 5 locations. Mid-season injury was 10% or less at all locations with fomesafen at 490 g ha -1 or less. Plant heights were reduced 11 to 29% in Georgia and North Carolina when fomesafen was applied at rates greater than 420 g ha -1 . In Tennessee, heights were reduced 8% with fomesafen at 560 g ha -1 . Compared to the non-treated control, plant stands were reduced 23 to 28% only in North Carolina when fomesafen rates exceeded 350 g ha -1 . Lint yields followed trends in plant stand, with yield being reduced 23 to 25% by fomesafen at 560 to 840 g ha -1 only in