gebhart/patrepeval huggingface dataset:
Evolutionarily Conserved Promoter Region Containing CArG*-Like Elements Is Crucial for Smooth Muscle Myosin Heavy Chain Gene Expression (1998)

In recent years, significant progress has been made toward understanding skeletal muscle development. However, the mechanisms that regulate smooth muscle development and differentiation are presently unknown. To better understand smooth muscle-specific gene expression, we have focused our studies on the smooth muscle myosin heavy chain (SMHC) gene, a highly specific marker of differentiated smooth muscle cells. The goal of the present study was to isolate and characterize the mouse SMHC gene promoter, since the mouse promoter would be particularly suited for in vivo promoter analyses in transgenic mice and would serve as a tool for targeting genes of interest into smooth muscle cells. We report here the isolation and characterization of the mouse SMHC promoter and its 5' flanking region. DNA sequence analysis of a 2.6-kb portion of the promoter identified several potential binding sites for known transcription factors. Transient transfection analysis of promoter deletion constructs in primary cultures of smooth muscle cells showed that the region between -1208 and -1050 bp is critical for maximal SMHC promoter activity. A comparison of SMHC promoter sequences from mouse, rat, and rabbit revealed the presence of a highly conserved region located between -967 and -1208 bp. This region includes three CArG/CArG*-like elements, two SP-1 binding sites, a NF-1-like element, an Nkx2-5 binding site, and an Elk-1 binding site. Gel mobility shift assay and DNase I footprinting analyses show that all three CArG/CArG*-like elements can form DNA-protein complexes with nuclear extract from vascular smooth muscle cells. Protein binding to the CArG* elements can be competed out by either serum response element or by an authentic CArG element from the cardiac alpha-actin gene. Using a serum response factor (SRF) antibody, we demonstrate that SRF is part of the protein complex. In addition, we show that cotransfection with the SRF dominant-negative mutant expression vector abolishes SMHC promoter activity, suggesting that SRF protein plays a critical role in SMHC gene regulation.
mRNA capping enzyme is recruited to the transcription complex by phosphorylation of the RNA polymerase II carboxy-terminal domain (1997)

Capping of mRNA occurs shortly after transcription initiation, preceding other mRNA processing events such as mRNA splicing and polyadenylation. To determine the mechanism of coupling between transcription and capping, we tested for a physical interaction between capping enzyme and the transcription machinery. Capping enzyme is not stably associated with basal transcription factors or the RNA polymerase II (Pol II) holoenzyme. However, capping enzyme can directly and specifically interact with the phosphorylated form of the RNA polymerase carboxy-terminal domain (CTD). This association occurs in the context of the transcription initiation complex and is blocked by the CTD-kinase inhibitor H8. Furthermore, conditional truncation mutants of the Pol II CTD are lethal when combined with a capping enzyme mutant. Our results provide in vitro and in vivo evidence that capping enzyme is recruited to the transcription complex via phosphorylation of the RNA polymerase CTD.
Astrocyte Growth, Reactivity, and the Target of the Antiproliferative Antibody, TAPA (1996)

Reactive astrocytes form a scar after injury to the CNS that many investigators believe contributes to the lack of functional regeneration. In the present study, we identify an astrocytic membrane protein that appears to play an important role in reactive gliosis and scar formation. Cultures of rat astrocytes were used as a model system to produce and to screen monoclonal antibodies that would alter cell growth. One antibody, AMP1, was identified that depresses the mitotic activity of cultured glial cells and alters their morphology. Expression cloning reveals that the antigen on the external surface of the cultured glial cells has a high degree of homology with the human lymphocyte protein called Target of the Anti-Proliferative Antibody (TAPA-1; this rat protein will be referred to as rTAPA). rTAPA is a member of the tetramembrane-spanning superfamily of proteins and, as with other members of this family of proteins, rTAPA is associated with the regulation of cellular interactions and mitotic activity. After an injury to the cerebral cortex, there is a dramatic increase in AMP1 immunoreactivity that is spatially restricted to the reactive astrocytes at the glial scar. This change represents an upregulation of a membrane protein, rTAPA, that is approximately equal to the increase observed for glial fibrillary acidic protein. The high levels of rTAPA at the site of CNS injury and the AMP1 antibody perturbation studies indicate that rTAPA may play a prominent role in the response of astrocytes to injury and in glial scar formation.
Implementation of a 4&lt;tex&gt;$times$&lt;/tex&gt;4 Switch With Passive Interconnects (2005)

We designed and fabricated a 4 /spl times/ 4 switch in which all interconnections were implemented using passive transmission lines (PTLs). The switch consisted of four identical 2 /spl times/ 2 switches connected using PTLs. The 2 /spl times/ 2 switch was designed using gate-to-gate passive interconnections. Using the on-chip testing method, we demonstrated 40-GHz operation of the 4 /spl times/ 4 switch. To verify the effectiveness of passive interconnection, we compared the 4 /spl times/ 4 switch with an identical switch that was designed using Josephson transmission lines (JTLs) for interconnections. The comparison showed that the PTL-version 4 /spl times/ 4 switch had 50% fewer junctions and required 55% less powering current. The latency and the largest jitter in the PTL-version 4 /spl times/ 4 switch were estimated to be 36% and 61%, respectively, of those of the JTL version.
Efficacy of cilofungin therapy administered by continuous intravenous infusion for experimental disseminated candidiasis in rabbits (1992)

Cilofungin has potent in vitro activity against Candida albicans, but previous in vivo models using twice daily intermittent dosing regimens have not consistently demonstrated in vivo efficacy. Because of the pharmacokinetics of cilofungin in rabbits, it has been suggested that administration by continuous intravenous infusion might be more effective. We compared the in vivo efficacy of continuous intravenous infusion of cilofungin with that of amphotericin B in a rabbit model of disseminated candidiasis. Cilofungin prepared as previously described in phosphate-buffered 33% polyethylene glycol was lethal to infected rabbits in this model, as was phosphate-buffered 33% polyethylene glycol alone. In contrast, cilofungin in 26% polyethylene glycol and sterile water administered by continuous intravenous infusion was tolerated by rabbits, was significantly more effective than amphotericin therapy in reducing candida colony counts in kidney tissue, and was as effective as amphotericin therapy in lung and spleen tissue and in cardiac valvular vegetations. The dosage regimen and diluent used in some previous studies may have adversely affected outcome of treatment with cilofungin.
Large-amplitude coherent spin waves excited by spin-polarized current in nanoscale spin valves (2007)

We present spectral measurements of spin-wave excitations driven by direct spin-polarized current in a free layer of nanoscale ${\mathrm{Ir}}_{20}{\mathrm{Mn}}_{80}∕{\mathrm{Ni}}_{80}{\mathrm{Fe}}_{20}∕\mathrm{Cu}∕{\mathrm{Ni}}_{80}{\mathrm{Fe}}_{20}$ spin valves. The measurements reveal that large-amplitude coherent spin-wave modes are excited over a wide range of bias current. The frequency of these excitations exhibits a series of jumps as a function of current due to transitions between different localized nonlinear spin-wave modes of the ${\mathrm{Ni}}_{80}{\mathrm{Fe}}_{20}$ nanomagnet. We find that micromagnetic simulations employing the Landau-Lifshitz-Gilbert equation of motion augmented by the Slonczewski spin-torque term (LLGS) accurately describe the frequency of the current-driven excitations including the mode transition behavior. However, LLGS simulations give qualitatively incorrect predictions for the amplitude of excited spin waves as a function of current.
OUM - A 180 nm nonvolatile memory cell element technology for stand alone and embedded applications (2002)

This paper discusses the development status of the memory cell element of OUM (Ovonic Unified Memory) - a chalcogenide-based, phase-change nonvolatile semiconductor memory technology at the 180 nm technology node. The device structure and characterization of the memory element will be reviewed. The key characteristics of the technology will be discussed for ultra-high density, low voltage, high-speed programming, high cycle count, high read speed, and competitive cost structure nonvolatile memory for stand alone and embedded applications. This technology is inherently radiation resistant and is bit byte or word programmable without the requirement of Flash-like block erase. Low voltage and energy operation make OUM an attractive candidate for mobile applications.
Single-Molecule Studies of Heterogeneous Dynamics in Polymer Melts Near the Glass Transition (2001)

Single-molecule spectroscopy was used to follow the orientation of a single probe molecule in a polymer film in real time. Broad spatially heterogeneous dynamics were observed on long time scales, which result from simple diffusive rotational motions on short time scales. This diffusive behavior persists for many rotations before the molecule's local environment changes to one characterized by a new time scale. This environmental exchange occurs instantaneously on the time scale of the experiment and may arise from large-scale collective motions. The distribution of exchange times for these environments was measured for several temperatures near the glass transition.
Intramyocardial Transplantation of Autologous Myoblasts : Can Tissue Processing Be Optimized? (2000)

Cell culture remains mandatory for SM transplantation to be successful but, in a clinical perspective, this process can be made more expeditious by preharvest muscle conditioning with bupivacaine, which greatly enhances the baseline cell yield.
Pd(II)-Catalyzed Pyridine N-Oxides Directed Arylation of Unactivated Csp3–H Bonds (2015)

A novel Pd(II)-catalyzed pyridine N-oxide directed remote arylation of unactivated Csp(3)-H bonds in aliphatic amides with aryl iodides has been developed. This protocol allows installing various aryl groups at the β- or γ-Csp(3) atom of alkyl carboxylic acid amides. The key palladabicyclic intermediate of this transformation has been identified by HR-MS and (1)H NMR method.
Prevalence of Alzheimer's disease in a community population of older persons. Higher than previously reported. (1989)

Clinically diagnosed Alzheimer's disease and other dementing illnesses were assessed in a geographically defined US community. Of 3623 persons (80.8% of all community residents over 65 years of age) who had brief memory testing in their homes, a stratified sample of 467 persons underwent neurological, neuropsychological, and laboratory examination. Prevalence rates of Alzheimer's disease were calculated for the community population from the sample undergoing clinical evaluation. Of those over the age of 65 years, an estimated 10.3% (95% confidence limits, 8.1% and 12.5%) had probable Alzheimer's disease. This prevalence rate was strongly associated with age. Of those 65 to 74 years old, 3.0% (95% confidence limits, 0.8 and 5.2) had probable Alzheimer's disease, compared with 18.7% (95% confidence limits, 13.2 and 24.2) of those 75 to 84 years old and 47.2% (95% confidence limits, 37.0 and 63.2) of those over 85 years. Other dementing conditions were uncommon. Of community residents with moderate or severe cognitive impairment, 84.1% had clinically diagnosed Alzheimer's disease as the only probable diagnosis. These data suggest that clinically diagnosed Alzheimer's disease is a common condition and that its public health impact will continue to increase with increasing longevity of the population.
Prevention of Atrial Fibrillation by Bucindolol Is Dependent on the Beta 1 389 Arg/Gly Adrenergic Receptor Polymorphism (2013)

Bucindolol prevented new-onset AF; β₁ and α(2c) polymorphisms predicted therapeutic response; and the 47% of patients who were β₁389 Arg homozygotes had an enhanced effect size of 74%. (Beta-Blocker Evaluation in Survival Trial [BEST]; NCT00000560)
Enhancer-Mediated Control of Macrophage-Specific Arginase I Expression (2004)

Arginase I expression in the liver must remain constant throughout life to eliminate excess nitrogen via the urea cycle. In contrast, arginase I expression in macrophages is silent until signals from Th2 cytokines such as IL-4 and IL-13 are received and the mRNA is then induced four to five orders of magnitude. Arginase I is hypothesized to play a regulatory and potentially pathogenic role in diseases such as asthma, parasitic, bacterial, and worm infections by modulating NO levels and promoting fibrosis. We show that Th2-inducible arginase I expression in mouse macrophages is controlled by an enhancer that lies -3 kb from the basal promoter. PU.1, IL-4-induced STAT6, and C/EBPbeta assemble at the enhancer and await the effect of another STAT6-regulated protein(s) that must be synthesized de novo. Identification of a powerful extrahepatic regulatory enhancer for arginase I provides potential to manipulate arginase I activity in immune cells while sparing liver urea cycle function.
Protected silver coatings for flashlamp-pumped Nd:glass amplifiers (1999)

A durable protected silver coating was designed and fabricated for possible use on flashlamp reflectors in the National Ignition Facility to avoid tarnishing under corrosive conditions and intense visible light. This coating provides a valuable alternative for mirror coatings where high reflectance and durability are important requirements. This paper describes a protected silver coating having high reflectance from 400 nm to 10,000 nm. The specular reflectance is between 95 percent and 98 percent in the visible region and 98 percent or better in the IR region.
Clinical experience of bendamustine in relapsed or refractory Hodgkin lymphoma: a retrospective analysis of the French compassionate use program in 28 patients (2013)

Limited data support the use of bendamustine in Hodgkin lymphoma (HL). This retrospective study evaluated the efficacy and toxicity of bendamustine in 28 patients with refractory HL or relapsed HL after autologous stem cell transplant (ASCT) used as part of a compassionate use program. The median number of therapies before bendamustine was 5 (3-8). ASCT and non-myeloablative allogeneic transplant were previously performed for 25 and six patients, respectively. The median number of bendamustine cycles administered was 3 (1-12). The objective response rate was 50% with complete response (CR) in 29% of patients. The median progression-free survival was 5.7 months, and 10.2 months in patients with CR. During the first six cycles, two patients had a febrile neutropenia and four patients had grade 3-4 thrombocytopenia. Bendamustine was effective in these highly pretreated patients with HL. It might be used earlier in the treatment strategy of HL and in combination with other active drugs.
An insight into the mechanism of inhibition of unusual bi-subunit topoisomerase I fromLeishmania donovaniby 3,3′-di-indolylmethane, a novel DNA topoisomerase I poison with a strong binding affinity to the enzyme (2007)

DIM (3,3'-di-indolylmethane), an abundant dietary component of cruciferous vegetables, exhibits a wide spectrum of pharmacological properties. In the present study, we show that DIM is a potent inhibitor of Leishmania donovani topoisomerase I with an IC50 of 1.2 microM. Equilibrium dialysis shows that DIM binds strongly to the free enzyme with a binding constant of 9.73x10(-9) M. The binding affinity of DIM to the small subunit is 8.6-fold more than that of the large subunit of unusual LdTOP1LS (bi-subunit L. donovani topoisomerase I). DIM stabilizes topoisomerase I-DNA cleavage complexes in vitro and also in vivo. Like CPT (camptothecin), DIM inhibits the religation step when the drug was added to preformed topoisomerase I-DNA binary complex. Hence, DIM is similar to CPT with respect to its ability to form the topoisomerase I-mediated 'cleavable complexes' in vitro and in vivo. But unlike CPT, DIM interacts with both free enzyme and substrate DNA. Therefore DIM is a non-competitive class I inhibitor of topoisomerase I. DIM also inhibits the relaxation activity of the CPT-resistant mutant enzyme LdTOP1Delta39LS (N-terminal deletion of amino acids 1-39 of LdTOP1LS). The IC50 values of DIM in simultaneous and enzyme pre-incubation relaxation assays were 3.6 and 2.9 muM respectively, which are higher than that of wild-type topoisomerase I (LdTOP1LS), indicating that the affinity of DIM to LdTOP1Delta39LS is less than that for LdTOP1LS. This is the first report on DIM as an L. donovani topoisomerase I poison. Our study illuminates a new mode of action of enzyme inhibition by DIM that might be exploited for rational drug design in human leishmaniasis.
Terminal amino acid sequences and proteolytic cleavage sites of mouse mammary tumor virus env gene products (1983)

The mature envelope glycoproteins of mouse mammary tumor virus (gp52 and gp36) were isolated by reversed-phase high-pressure liquid chromatography. The N-terminal amino acid sequence of gp36 was determined for 28 residues. The C-terminal amino acid sequences of gp52 and gp36 were determined by carboxypeptidase digestion. The N-terminal amino acid sequence of gp52 has been reported previously (L. O. Arthur et al., J. Virol. 41:414-422, 1982). These data were aligned with the predicted amino acid sequence of the env gene product obtained by translation of the DNA sequence (S. M. S. Redmond and C. Dickson, Eur. Mol. Biol. Org. J. 2:125-131, 1983). The amino acid sequences of the mature viral proteins were in agreement with the predicted amino acid sequence of the env gene product over the regions of alignment. This alignment showed the sites of proteolytic cleavages of the env gene product leading to the mature viral envelope glycoproteins. The N-terminal amino acid sequence of gp52 starts at residue 99 of the predicted structure indicating proteolytic cleavage of a signal peptide. A dipeptide (Lys-Arg) is excised between the C-terminus of gp52 and the N-terminus of gp36. The C-terminal amino acid sequence of gp36 is identical to the sequence predicted by the codons immediately preceding the termination codon for the env gene product. The data show that there is no proteolytic processing at the C-terminal of the murine mammary tumor virus env gene product and that the env gene coding region extends into the long terminal repeat.
Characterization of saturable binding sites for circulating pancreatic polypeptide in rat brain (1990)

Pancreatic polypeptide (PP) inhibits pancreatic exocrine secretion by indirect mechanisms that may be centrally mediated. The central site of action of PP that results in inhibition of pancreatic secretion has not been identified. Using autoradiography to identify 125I-PP binding to frozen sections of rat brain, we have identified saturable, high-affinity PP receptors in high concentrations in the interpenduncular nucleus, area postrema (AP), nucleus tractus solitarius, and dorsal motor nucleus of the vagus. The PP receptor differs from neuropeptide Y and peptide YY receptors in its binding specificity and location. Because PP is not produced in the brain, and the blood-brain barrier (BBB) excludes circulating peptides from most areas in the brain, we employed an in vivo radioreceptor assay to determine whether circulating PP binds to areas such as the AP that has both an incomplete BBB and a high concentration of PP receptors. 125I-PP and 131I-bovine serum albumin were infused simultaneously into rats through a peripheral vein with or without excess unlabeled PP. After 10 min, rats were killed and the brains were removed and cut into eight regions based on the autoradiographic localization of PP receptors. There was a significant (P less than 0.02) increase in saturable radiolabeled PP accumulation in the region that included the AP, demonstrating that circulating PP can bind to this area of the brain in vivo. PP is released into the circulation after a meal via mechanisms that exhibit vagal and cholinergic dependence. We speculate that PP completes a feedback loop by binding to receptors in the AP and interacting with the adjacent vagal nuclei to inhibit vagal activity.
PROTECTION AGAINST ULTRAVIOLET B RADIATION‐INDUCED EFFECTS IN THE SKIN OF SKH‐1 HAIRLESS MICE BY A POLYPHENOLIC FRACTION ISOLATED FROM GREEN TEA (1993)

In prior studies we and others have shown that oral feeding of a polyphenolic fraction isolated from green tea (GTP) or water extract of green tea affords protection against ultraviolet B (UVB) radiation-induced carcinogenesis in SKH-1 hairless mice (Wang et al., Carcinogenesis 12, 1527-1530, 1991). It is known that exposure of murine skin to UVB radiation results in cutaneous edema, depletion of the antioxidant-defense system and induction of ornithine decarboxylase (ODC) and cyclooxygenase activities. In this study we assessed the protective effect of GTP on these UVB radiation-caused changes in murine skin. Oral feeding of 0.2% GTP (wt/vol) as the sole source of drinking water for 30 days to SKH-1 hairless mice followed by irradiation with UVB (900 mJ/cm2) resulted in significant protection against UVB radiation-caused cutaneous edema (P < 0.0005) and depletion of the antioxidant-defense system in epidermis (P < 0.01-0.02). The oral feeding of GTP also resulted in significant protection against UVB radiation-caused induction of epidermal ODC (P < 0.005-0.01) and cyclooxygenase activities (P < 0.0001) in a time-dependent manner. Our data indicate that the inhibition of UVB radiation-caused changes in these markers of tumor promotion in murine skin by GTP may be one of the possible mechanisms of chemopreventive effects associated with green tea against UVB-induced tumorigenesis. The results of this study suggest that green tea, specifically polyphenols present therein, may be useful against inflammatory responses associated with the exposure of skin to solar radiation.
A Transmembrane Form of the Prion Protein Contains an Uncleaved Signal Peptide and Is Retained in the Endoplasmic Reticululm (2001)

Although there is considerable evidence that PrP(Sc) is the infectious form of the prion protein, it has recently been proposed that a transmembrane variant called (Ctm)PrP is the direct cause of prion-associated neurodegeneration. We report here, using a mutant form of PrP that is synthesized exclusively with the (Ctm)PrP topology, that (Ctm)PrP is retained in the endoplasmic reticulum and is degraded by the proteasome. We also demonstrate that (Ctm)PrP contains an uncleaved, N-terminal signal peptide as well as a C-terminal glycolipid anchor. These results provide insight into general mechanisms that control the topology of membrane proteins during their synthesis in the endoplasmic reticulum, and they also suggest possible cellular pathways by which (Ctm)PrP may cause disease.