gebhart/patrepeval huggingface dataset:
Promoter and operator determinants for fur-mediated iron regulation in the bidirectional fepA-fes control region of the Escherichia coli enterobactin gene system (1994)

The fepA-entD and fes-entF operons in the enterobactin synthesis and transport system are divergently transcribed from overlapping promoters, and both are inhibited by the Fur repressor protein under iron-replete conditions. A plasmid harboring divergent fepA'-phoA and fes-entF'-'lacZ fusions, both under the control of this bidirectional regulatory region, was constructed for the purpose of monitoring changes in expression of the two operons simultaneously. Deletion analysis, site-directed mutagenesis, and primer extension were employed to define both a single promoter governing the expression of fes-entF and two tandemly arranged promoters giving rise to the opposing fepA-entD transcript. A single Fur-binding site that coordinately regulates the expression of all transcripts emanating from this control region was identified by in vitro protection from DNase I nicking. The substitution of one base pair in the Fur recognition sequence relieved Fur repression but did not change the in vitro affinity of Fur for its binding site. Additional mutations in a limited region outside of the promoter determinants for either transcript inhibited expression of both fes and fepA. These observations suggest a mechanism of Fur-mediated regulation in this compact control region that may involve other regulatory components.
Approaches to Utilize Mesenchymal Progenitor Cells as Cellular Vehicles (2003)

Mammalian cells represent a novel vector approach for gene delivery that overcomes major drawbacks of viral and nonviral vectors and couples cell therapy with gene delivery. A variety of cell types have been tested in this regard, confirming that the ideal cellular vector system for ex vivo gene therapy has to comply with stringent criteria and is yet to be found. Several properties of mesenchymal progenitor cells (MPCs), such as easy access and simple isolation and propagation procedures, make these cells attractive candidates as cellular vehicles. In the current work, we evaluated the potential utility of MPCs as cellular vectors with the intent to use them in the cancer therapy context. When conventional adenoviral (Ad) vectors were used for MPC transduction, the highest transduction efficiency of MPCs was 40%. We demonstrated that Ad primary-binding receptors were poorly expressed on MPCs, while the secondary Ad receptors and integrins presented in sufficient amounts. By employing Ad vectors with incorporated integrin-binding motifs (Ad5lucRGD), MPC transduction was augmented tenfold, achieving efficient genetic loading of MPCs with reporter and anticancer genes. MPCs expressing thymidine kinase were able to exert a bystander killing effect on the cancer cell line SKOV3ip1 in vitro. In addition, we found that MPCs were able to support Ad replication, and thus can be used as cell vectors to deliver oncolytic viruses. Our results show that MPCs can foster expression of suicide genes or support replication of adenoviruses as potential anticancer therapeutic payloads. These findings are consistent with the concept that MPCs possess key properties that ensure their employment as cellular vehicles and can be used to deliver either therapeutic genes or viruses to tumor sites.
[Role of BCG in T1G3 bladder transitional cell carcinoma (TCC): our experience]. (1996)

High grade superficial TCC of the bladder (T1 G3) has an important risk of recurrence and/or progression (40%) after TUR-B and a low survival rate (57% at 3 years, 50% at 10 years). Intravescical treatment with BCG seems to be able to reduce these rates. 64 patients with T1 G3 vescical TCC underwent a "second look" TUR-B. 9/64 patients presented locally advanced tumor (T2-3) or persistent high risk superficial TCC (T1 G3 + Tis) and underwent to early cistectomy. BCG intravescical therapy has been performed in the remaining 55 patients: 10 of them had not been evaluated because local or sistemic toxicity and consequent early interruption of treatment. BCG Pasteur was given weekly at the dose of 75 mg for two cycles of 6 weeks with a rest period of 6 weeks between the two cycles and then monthly for one year and every three months during next two years too. After the first 6 weeks 43/45 patients resulted tumor-free and 2/45 presented persistent Tis: after the second 6 weeks-cycle of BCG, two other patients had evidence of vescical TCC (one T2 G3 and the other T1 G3); all these four patients were submitted to radical cystectomy or radiotherapy. Of the reamining 41 patients, 28 presented had no recurrences, nowadays living and tumor-free; 3 presented local neoplastic progression and dead; relapsed in T1 G2 and are living NED after local chemotherapy. At a mean follow-up of 18 months, the total amount of recurrences is 17/45 (38%), progression rate is 4/45 (8.8%), exitus 5/45 (11%) and living NED are 28/45 (62%). In our opinion local BCG treatment for T1 G3 bladder cancer, after TUR--B, seems to be able to reduce the risk of recurrence and mortality.
Genetics of Parkinson disease and other movement disorders (2012)

New genes have been implicated in Parkinson disease and other movement disorders through the use of NGS. The identification of risk variants has been facilitated by GWAS and meta-analyses. Furthermore, new models are being developed to study the molecular mechanisms involved in the pathogenesis of these diseases.
Purification and Characterization of GP90, One of the Envelope Glycoproteins of Respiratory Syncytial Virus (1984)

The large glycoprotein, GP90, of respiratory syncytial virus (RSV) was purified by affinity chromatography using a monoclonal antibody. Hyperimmune rabbit antiserum directed specifically to the purified GP90 neutralized RSV to high titre but did not inhibit fusion of previously infected cells. 125I-labelled GP90 bound rapidly to HEp-2 cells in an unsaturable manner; binding was inhibited by the hyperimmune rabbit antiserum.
High speed Flash Memory and 1T-DRAM on dopant segregated Schottky barrier (DSSB) FinFET SONOS device for multi-functional SoC applications (2008)

A novel dopant segregated Schottky barrier (DSSB) FinFET SONOS device is demonstrated in terms of multi functioning in a high speed NAND-type flash memory and capacitorless 1T-DRAM. In addition, a novel program mechanism that uses energy band engineered hot electrons (EBEHE) energized by sharp energy band bending at the edge of source/drain (S/D) is proposed for a high speed flash memory programming operation. A short program time of 100 ns and a low program voltage of 12 V yield a V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">th</sub> shift of 3.5 V and a retention time exceeding 10 years. For multi functioning, the operation of a capacitorless 1T-DRAM is also demonstrated with a partially silicided DSSB in the same device.
High Performance Power MOSFETs with Strained-Si Channel (2005)

To improve a current drivability and an on-resistance characteristic of the high voltage MOSFET, we propose a novel power MOSFET employing a strained-Si channel structure. A 20nm thick strained-Si low field channel NMOSFET with a 0.75/spl mu/m thick Si/sub 0.8/Ge/sub 0.2/ buffer layer improved the drive current by 20% with a 25% reduction in on-resistance compared with conventional Si channel high voltage NMOSFET, while suppressing breakdown voltage and subthreshold slope characteristic degradation by 6% and 8% respectively. Also, the strained-Si high voltage NMOSFET improved the transconductance by 28% and 52% at linear and saturation regime.
A human endogenous retroviral sequence encoding an antigen recognized on melanoma by cytolytic T lymphocytes. (2002)

We have identified a gene encoding an antigen recognized by cytolytic T lymphocytes on the autologous tumor cells of a melanoma patient, AVL3. The gene shows homologies with members of the HERV-K family of human endogenous retroviruses, and it was provisionally named HERV-K-MEL. It contains many mutations that disrupt the open reading frames coding for all of the viral proteins. The HERV-K-MEL gene is not expressed in normal tissues with the exception of testis and some skin samples. It is expressed in most samples of cutaneous and ocular melanoma. It is also expressed in a majority of naevi and in a minority of carcinomas and sarcomas. The antigenic peptide, presented by HLA-A2 molecules, is encoded by a very short open reading frame present in the env region of a spliced HERV-K-MEL transcript. Anti-HERV.A2 CTLp could not be detected in the blood of three individuals without cancer but were present at a frequency of 3 x 10(-5) among blood CD8 T cells in patient AVL3 and 6 x 10(-7) in another HLA-A2 melanoma patient whose tumor expressed HERV-K-MEL. Anti-HERV.A2 CTL clones derived from each patient lysed melanoma cells. Analysis of T-cell receptor beta chain sequences indicated that the anti-HERV.A2 CTL population was oligoclonal in patient AVL3 and probably monoclonal in the other patient. These results suggest that HERV-K-MEL is a source of antigens that are targeted by CTLs in melanoma patients and could therefore be used for vaccination.
Meta-Scheduling For Distributed Continuous Media (1990)

Next-generation distributed systems will support continuous media (digital audio and video) in the same hardware/software framework as other data. Many applications that use continuous media (CM) have end-to-end performance requirements such as minimum throughput or maximum delay. To reliably support these requirements, system components such as CPU schedulers, networks, and file systems must offer realtime semantics. A meta-scheduler coordinates these components, negotiating end-to-end guarantees on behalf of clients. The CM-resource model, described in this paper, provides a basis for such a meta-scheduler. The model defines a workload parameterization, an abstract interface to resources, and an end-to-end algorithm for negotiated reservation of multiple resources; the division of delay is based on an economic model. Clients make reservations for worst-case workload and resources offer hard delay bounds. However, system components may "work ahead" within limits, increasing the responsiveness of bursty non-realtime workload
The cognitive coprocessor architecture for interactive user interfaces (1989)

The graphics capabilities and speed of current hardware systems allow the exploration of 3D and animation in user interfaces, while improving the degree of interaction as well. In order to fully utilize these capabilities, new software architectures must support multiple, asynchronous, interacting agents (the Multiple Agent Problem), and support smooth interactive animation (the Animation Problem). The Cognitive Coprocessor is a new user interface architecture designed to solve these two problems, while supporting highly interactive user interfaces that have 2D and 3D animations. This architecture includes 3D Rooms, a 3D analogy to the Rooms system with Rooms Buttons extended to Interactive Objects that deal with 3D, animation, and gestures. This research is being tested in the domain of Information Visualization, which uses 2D and 3D animated artifacts to represent the structure of information. A prototype, called the Information Visualizer, has been built.
Immune escape of tumors: apoptosis resistance and tumor counterattack (2002)

Interactions between the immune system and malignant cells play an important role in tumorigenesis. Failure of the immune system to detect and reject transformed cells may lead to cancer development. Tumors use multiple mechanisms to escape from immune-mediated rejection. Many of these mechanisms are now known on a cellular and molecular level. Despite this knowledge, cancer immunotherapy is still not an established treatment in the clinic. This review discusses the immune escape mechanisms used by tumors with an emphasis on mechanisms related to apoptosis.
Dietary Casein and Soy Protein Isolate Modulate the Effects of Raffinose and Fructooligosaccharides on the Composition and Fermentation of Gut Microbiota in Rats (2016)

Although diet has an important influence on the composition of gut microbiota, the impact of dietary protein sources has only been studied to a minor extent. In this study, we examined the influence of different dietary protein sources regarding the effects of prebiotic oligosaccharides on the composition and metabolic activity of gut microbiota. Thirty female rats were fed casein and soy protein isolate with cellulose, raffinose (RAF), and fructooligosaccharides (FOS). Microbiota composition was examined by real-time qPCR and denaturing gradient gel electrophoresis. Dietary protein source affected cecum microbiota; acetic acid concentration and Lactobacillus spp. populations were greater with soy protein than with casein. Prebiotic oligosaccharides had distinctive effects on gut microbiota; RAF increased the acetic acid concentration and Bifidobacterium spp. populations, and FOS increased the butyric acid concentration regardless of the dietary protein. Likewise, Bifidobacterium sp., Collinsella sp., and Lactobacillus sp. were detected in microbiota of the rats fed RAF, and Bacteroides sp., Roseburia sp., and Blautia sp. were seen in microbiota of the rats fed FOS. Interactions between dietary proteins and prebiotic oligosaccharides were observed with Clostridium perfringens group populations and cecum IgA concentration. RAF and FOS decreased C. perfringens group populations in casein-fed rats, and the combination of soy protein and RAF substantially increased cecum IgA concentration. These results indicate that dietary proteins can differentially modulate the effects of prebiotic oligosaccharides on gut fermentation and microbiota, depending on the type of carbohydrate polymers involved.
A Phase I Dose Escalation and Expansion Study of the Anticancer Stem Cell Agent Demcizumab (Anti-DLL4) in Patients with Previously Treated Solid Tumors (2014)

Demcizumab was generally well tolerated at doses ≤5 mg weekly with disease stabilization and decreases in tumor size demonstrating antitumor activity. Hypertension was the most common adverse event that was clearly related to treatment. Prolonged administration was associated with an increased risk of congestive heart failure.
Effect of Dexmedetomidine on Preventing Postoperative Agitation in Children: A Meta-Analysis (2015)

Dexmedetomidine was proved effective for preventing EA and for reducing severe pain and the requirement of rescue drugs. It slightly increased the time to eye-open and the time to PACU discharge. Dexmedetomidine was also more beneficial than propofol or fentanyl in preventing EA.
Anle138b: a novel oligomer modulator for disease-modifying therapy of neurodegenerative diseases such as prion and Parkinson’s disease (2013)

In neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and prion diseases, deposits of aggregated disease-specific proteins are found. Oligomeric aggregates are presumed to be the key neurotoxic agent. Here we describe the novel oligomer modulator anle138b [3-(1,3-benzodioxol-5-yl)-5-(3-bromophenyl)-1H-pyrazole], an aggregation inhibitor we developed based on a systematic high-throughput screening campaign combined with medicinal chemistry optimization. In vitro, anle138b blocked the formation of pathological aggregates of prion protein (PrP(Sc)) and of α-synuclein (α-syn), which is deposited in PD and other synucleinopathies such as dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). Notably, anle138b strongly inhibited all prion strains tested including BSE-derived and human prions. Anle138b showed structure-dependent binding to pathological aggregates and strongly inhibited formation of pathological oligomers in vitro and in vivo both for prion protein and α-synuclein. Both in mouse models of prion disease and in three different PD mouse models, anle138b strongly inhibited oligomer accumulation, neuronal degeneration, and disease progression in vivo. Anle138b had no detectable toxicity at therapeutic doses and an excellent oral bioavailability and blood-brain-barrier penetration. Our findings indicate that oligomer modulators provide a new approach for disease-modifying therapy in these diseases, for which only symptomatic treatment is available so far. Moreover, our findings suggest that pathological oligomers in neurodegenerative diseases share structural features, although the main protein component is disease-specific, indicating that compounds such as anle138b that modulate oligomer formation by targeting structure-dependent epitopes can have a broad spectrum of activity in the treatment of different protein aggregation diseases.
PROTEIN PRENYLATION: GENES, ENZYMES, TARGETS, AND FUNCTIONS (1992)

Orthologs and paralogs are two fundamentally different types of homologous genes that evolved, respectively, by vertical descent from a single ancestral gene and by duplication. Orthology and paralogy are key concepts of evolutionary genomics. A ...Read More
High-resolution EEG using spline generated surface Laplacians on spherical and ellipsoidal surfaces (1993)

Spline generated surface Laplacians are introduced as an effective method for estimating neocortical source activity at moderate scales. The method appears to be robust to the unavoidable perturbations of measured potentials and errors of head geometry and resistivity that are certain to occur in clinical or research settings. In particular, we have derived the surface Laplacian for general ellipsoidal surfaces in terms of the spline function. The spline-Laplacian accurately estimates isolated dipoles or distributed sources, is insensitive to subcortical sources and to sources which originate outside the boundaries of the electrode array, and acts as a bandpass spatial filter whose characteristics appear to provide a good match to the volume conduction of intracranial sources through human heads. As a result, spatial resolution is improved over that obtained with conventional EEG by at least a factor of three. This improvement, whether obtained with spline-Laplacian or model-dependent methods, is likely to have a significant impact on both medical and cognitive studies involving EEG.
Nucleotide and Amino Acid Sequence Analysis of the 100K Protein of a Serotype 3 Porcine Adenovirus (1997)

The genomic region between map units 69 and 78 of a type 3 porcine adenovirus (PAV3) was sequenced and analysed. An open reading frame (ORF) of 2514 nucleotides encoding a polypeptide of 838 amino acids and approximately 94.1 kDa was found. The size and location of the ORF suggested it was the PAV3 homo-logue of the 100K gene and this was confirmed by nucleotide sequence comparison with the 100K of human adenovirus type 2. Amino acid sequence alignment of the predicted polypeptide with the sequences of the 100K proteins of four human adenoviruses and type 10 fowl adenovirus revealed sequence identities of between 31% and 52%. Although amino acid conservation was present throughout the entire sequences compared, lower identity was noted in both the amino-and carboxy-termini.
Epigenetics, DNA Methylation, and Chromatin Modifying Drugs (2008)

Evidence is emerging that several diseases and behavioral pathologies result from defects in gene function. The best-studied example is cancer, but other diseases such as autoimmune disease, asthma, type 2 diabetes, metabolic disorders, and autism display aberrant gene expression. Gene function may be altered by either a change in the sequence of the DNA or a change in epigenetic programming of a gene in the absence of a sequence change. With epigenetic drugs, it is possible to reverse aberrant gene expression profiles associated with different disease states. Several epigenetic drugs targeting DNA methylation and histone deacetylation enzymes have been tested in clinical trials. Understanding the epigenetic machinery and the differential roles of its components in specific disease states is essential for developing targeted epigenetic therapy.
Converting Enzyme Determines Plasma Clearance of Angiotensin-(1–7) (1998)

We determined the mechanism accounting for the removal and metabolism of angiotensin-(1-7) [Ang-(1-7)] in 21 anesthetized spontaneously hypertensive (SHR), 18 age-matched normotensive Sprague-Dawley (SD), and 36 mRen-2 transgenic (TG+) rats. Animals of all 3 strains were provided with tap water or tap water containing losartan, lisinopril, or a combination of lisinopril and losartan for 2 weeks. On the day of the experiment, Ang-(1-7) was infused for a period of 15 minutes at a rate of 278 nmol . kg-1 . min-1. After this time, samples of arterial blood were collected rapidly at regular intervals for the assay of plasma Ang-(1-7) levels by radioimmunoassay. Infusion of Ang-(1-7) had a minimal effect on vehicle-treated SD rats but elicited a biphasic pressor/depressor response in vehicle-treated SHR and TG+ rats. In lisinopril-treated rats, Ang-(1-7) infusion increased blood pressure, whereas losartan treatment abolished the pressor component of the response without altering the secondary fall in arterial pressure. Combined treatment with lisinopril and losartan abolished the cardiovascular response to Ang-(1-7) in all 3 strains. In vehicle-treated SD, SHR and TG+ the half-life (t1/2) of Ang-(1-7) averaged 10+/-1, 10+/-1, and 9+/-1 seconds, respectively. Lisinopril alone or in combination with losartan produced a statistically significant rise in the half-life of Ang-(1-7) in all 3 strains of rats. Plasma clearance of Ang-(1-7) was significantly greater in the untreated SD rats compared with either the SHR or TG+ rat. Lisinopril treatment was associated with reduced clearance of Ang-(1-7) in all 3 strains. Concurrent experiments in pulmonary membranes from SD and SHR showed a statistically significant inhibition of 125I-Ang-(1-7) metabolism in the presence of lisinopril. These studies showed for the first time that the very short half-life of Ang-(1-7) in the circulation is primarily accounted for peptide metabolism by ACE. These findings suggest a novel role of ACE in the regulation of the production and metabolism of the two primary active hormones of the renin angiotensin system.
Performance driven multi-layer general area routing for PCB/MCM designs (1998)

In this paper we present a new global router appropriate for Multichip Module (MCM) and dense Printed Circuit Board (PCB) design, which utilizes a hybrid of the classical rip-up and reroute approach, and the more recent iterative deletion [9] method. The global router addresses performance issues by utilizing recent results in high performance interconnect design, while still effectively minimizing global congestion.