gebhart/patrepeval huggingface dataset:
The Role of the Medial Frontal Cortex in Cognitive Control (2004)

Adaptive goal-directed behavior involves monitoring of ongoing actions and performance outcomes, and subsequent adjustments of behavior and learning. We evaluate new findings in cognitive neuroscience concerning cortical interactions that subserve the recruitment and implementation of such cognitive control. A review of primate and human studies, along with a meta-analysis of the human functional neuroimaging literature, suggest that the detection of unfavorable outcomes, response errors, response conflict, and decision uncertainty elicits largely overlapping clusters of activation foci in an extensive part of the posterior medial frontal cortex (pMFC). A direct link is delineated between activity in this area and subsequent adjustments in performance. Emerging evidence points to functional interactions between the pMFC and the lateral prefrontal cortex (LPFC), so that monitoring-related pMFC activity serves as a signal that engages regulatory processes in the LPFC to implement performance adjustments.
Inhibitors of angiogenesis in a clinical perspective (1996)

Inhibition of angiogenesis or preventing the outgrowth of new blood vessels towards a tumor is one of the most promising areas of anticancer drug development. Several angiogenesis inhibitors are now on the verge of being tested in clinical trials. This review discusses possible applications of inhibitors of angiogenesis and whether the current methodologies for testing novel anticancer drugs are appropriate to evaluate the efficacy of inhibitors of angiogenesis.
Antitumor activity and pharmacokinetics of liposomes containing lipophilic gemcitabine prodrugs. (2007)

The incorporation of C18gem-prodrug in liposomes increased the plasma half life of the drug resulting in increased accumulation in the tumor cells and a higher level of antitumoral efficacy. The results obtained with different tumors sensitive to gemcitabine support the efficacy of this proposed drug delivery system.
A population of cholinergic neurons is present in the macaque monkey thalamus (1998)

Three new cholinergic markers were employed to study the cholinergic innervation in the thalamus of adult macaque monkeys. They were: two antibodies against choline acetyltransferase (ChAT), one polyclonal and one monoclonal; and a polyclonal antibody against the vesicular transporter of acetylcholine (VAChT), a powerful new marker that colocalizes with ChAT. This approach led to an unexpected finding: the three antibodies positively immunostained a population of neurons in the paracentral nucleus. The immunostained cells are confined to the dorsal region of this nucleus along its rostrocaudal extent. Measurement of the somatic areas of the immunostained neurons indicated that they correspond to a population of large neurons thought to be projection neurons. Because dorsal paracentral neurons are known to project to the dorsal striatum and specific cortical areas involved in visual and visuomotor mechanisms, these structures might be modulated by cholinergic thalamic neurons.
Trans -Activator Gene of Human T-Lymphotropic Virus Type III (HTLV-III) (1985)

Human T-lymphotropic virus type III (HTLV-III) encodes a trans-acting factor that activates the expression of genes linked to the HTLV-III long terminal repeat. By functional mapping of complementary DNA transcripts of viral messenger RNA's the major functional domain of the gene encoding this factor was localized to a region immediately before the env gene of the virus, a region previously thought to be noncoding. This newly identified gene consists of three exons, and its transcription into messenger RNA involves two splicing events bringing together sequences from the 5' part (287 base pairs), middle (268 base pairs), and 3'part (1258 base pairs) of the HTLV-III genome. A similar messenger RNA with a truncated second exon (70 base pairs) does not encode a trans-acting function. It is proposed that this second messenger RNA is the transcript of a gene (3'-orf) located after the env gene. Messenger RNA's were also identified for the env and gag-pol genes of HTLV-III.
Multonic Markov word models for large vocabulary continuous speech recognition (1993)

A new class of hidden Markov models is proposed for the acoustic representation of words in an automatic speech recognition system. The models, built from combinations of acoustically based sub-word units called fenones, are derived automatically from one or more sample utterances of a word. Because they are more flexible than previously reported fenone-based word models, they lead to an improved capability of modeling variations in pronunciation. They are therefore particularly useful in the recognition of continuous speech. In addition, their construction is relatively simple, because it can be done using the well-known forward-backward algorithm for parameter estimation of hidden Markov models. Appropriate reestimation formulas are derived for this purpose. Experimental results obtained on a 5000-word vocabulary natural language continuous speech recognition task are presented to illustrate the enhanced power of discrimination of the new models.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Genomics of cellulose biosynthesis in poplars (2004)

Genetic improvement of cellulose production in commercially important trees is one of the formidable goals of current forest biotechnology research. To achieve this goal, we must first decipher the enigmatic and complex process of cellulose biosynthesis in trees. The recent availability of rich genomic resources in poplars make Populus the first tree genus for which genetic augmentation of cellulose may soon become possible. Fortunately, because of the structural conservation of key cellulose biosynthesis genes between Arabidopsis and poplar genomes, the lessons learned from exploring the functions of Arabidopsis genes may be applied directly to poplars. However, regulation of these genes will most likely be distinct in these two-model systems because of their inherent biological differences. This research review covers the current state of knowledge about the three major cellulose biosynthesis-related gene families from poplar genomes: cellulose synthases, sucrose synthases and korrigan cellulases. Furthermore, we also suggest some future research directions that may have significant economical impacts on global forest product industries.
Complications of Intravesical Oxybutynin Chloride Therapy in the Pediatric Myelomeningocele Population (1997)

Untoward effects and inconvenience are the most common reasons for discontinuing intravesical oxybutynin chloride therapy for neurogenic bladder dysfunction. Children who previously had side effects from oral oxybutynin chloride are more likely to have them during intravesical therapy.
A Dithienyl Benzotriazole‐based Polyfluorene: Synthesis and Applications in Polymer Solar Cells and Red Light‐Emitting Diodes (2011)

Abstract A new donor–acceptor type polyfluorene derivative, poly[9,9‐dioctyl‐2,7‐fluorene‐alt‐(4,7‐bis(2′‐thienyl)‐2‐octyl‐2,1,3‐benzotriazole)] (PFDTBTz), is synthesized by a Suzuki cross‐coupling polymerization reaction. The optical, electrochemical, photovoltaic, and electroluminescence properties of PFDTBTz are investigated in detail. The maximum power conversion efficiency (PCE) of the PSCs based on PFDTBTz/PC 71 BM (1:2 w/w) reaches 2.1% with a short circuit current density ( J sc ) of 5.73 mA · cm −2 , an open circuit voltage ( V oc ) of 0.84 V, and a fill factor (FF) of 0.44 under AM 1.5G, 100 mW · cm −2 illumination. Polymer light‐emitting diodes (PLEDs) are fabricated in an ITO/PEDOT:PSS (30 nm)/PFDTBTz (60 nm)/BAlq (40 nm)/Cs 2 CO 3 :Ag configuration and light emission is observed at a voltage greater than 8.0 V. The EL device shows almost pure red and the efficiency is very stable when the current density is increased, making it useful for commercial applications. magnified image
A frequency hopping spread spectrum transmission scheme for uncoordinated cognitive radios (2009)

One of the major challenges to cognitive radios is the synchronization of distributed radios onto the same spectrum white spaces which vary in time and space. In this paper, we propose a frequency-hopping spread spectrum transmission scheme which works reliably without any a priori handshaking assumption. Each cognitive radio independently detects white spaces, and then selects one of them to transmit or receive signals according to a pre-defined frequency hopping pattern. While exploiting the reliability of the white space detection capability of cognitive radios, the new scheme is robust to even large detection errors. According to the accuracy of the spectrum sensing, both the secondary data rate and the interference to primary users can be optimized by adjusting the spreading gain. Its performance is analyzed and demonstrated by simulations.
Phase II trial of high-dose melphalan and autologous bone marrow transplantation for metastatic colon carcinoma. (1986)

Colon carcinoma, the second leading cause of cancer-related deaths in the United States, is resistant to chemotherapy in a large majority of cases. Single-agent and combination chemotherapy have failed to prolong survival. New approaches are clearly needed. In experimental models, a steep dose-response curve for colorectal cancer has been demonstrated using various agents. The hematopoietic toxicity of high-dose therapy with these drugs can be circumvented by autologous bone marrow transplantation. We investigated the use of high-dose melphalan with autologous bone marrow rescue in 20 patients with metastatic colon carcinoma. Each patient received melphalan, 180 mg/m2 intravenously (IV), followed eight hours later by bone marrow infusion. Median duration of granulocytopenia (less than 500 neutrophils/microL) was twelve days (range, 5 to 35 days), while transfusion-dependent thrombocytopenia (less than 20,000 platelets/microL) had a median duration of eight days (range, 3 to 23 days). Time to bone marrow engraftment was not affected by prior 5-fluorouracil therapy. Nausea and vomiting occurred in 14 patients but was generally short lived. Mild stomatitis, esophagitis, and diarrhea were common. Severe gastrointestinal (GI) side effects did not occur. One treatment-related death occurred secondary to intramural tumor necrosis, which resulted in massive lower GI bleeding. Complete responses were observed in three patients (15%) and partial responses in six patients (30%), for an overall response rate of 45%. Median survival was 198 days in this group of patients with extensive disease. High-dose melphalan therapy for metastatic colon carcinoma, when used with autologous bone marrow transplantation, appears to achieve a high response rate with tolerable toxicity. Further investigation is needed to define the role of this therapy in the care of advanced colon carcinoma.
Molecular Characterization of a Novel A Kinase Anchor Protein from Drosophila melanogaster (1997)

Activation of protein kinase A (PKA) at discrete intracellular sites facilitates oogenesis and development in Drosophila. Thus, PKA-anchor protein complexes may be involved in controlling these crucial biological processes. Evaluation of this proposition requires knowledge of PKA binding/targeting proteins in the fly. We now report the discovery and characterization of cDNAs encoding a novel, Drosophila A kinase anchor protein, DAKAP550. DAKAP550 is a large (>2300 amino acids) acidic protein that is maximally expressed in anterior tissues. It binds regulatory subunits (RII) of both mammalian and Drosophila PKAII isoforms. The tethering region of DAKAP550 includes two proximal, but non-contiguous RII-binding sites (B1 and B2). The B1 domain (residues 1406-1425) binds RII approximately 20-fold more avidly than B2 (amino acids 1350-1369). Affinity-purified anti-DAKAP550 IgGs were exploited to demonstrate that the anchor protein is expressed in many cells in nearly all tissues throughout the lifespan of the fly. However, DAKAP550 is highly enriched and asymmetrically positioned in subpopulations of neurons and in apical portions of cells in gut and trachea. The combination of RII (PKAII) binding activity with differential expression and polarized localization is consistent with a role for DAKAP550 in creating target loci for the reception of signals carried by cAMP. The DAKAP550 gene was mapped to the 4F1.2 region of the X chromosome; flies that carry a deletion for this portion of the X chromosome lack DAKAP550 protein.
Preference for a new prefilled insulin pen compared with the original pen (2011)

FT was found to be comparable to FP with respect to the efficacy and safety profile. Significantly more subjects favored the FT device in terms of ease of use, insulin injection, diabetes management, and overall preference. A limitation of the present study was its open-label design because the pen devices used to administer the insulin were distinctively different and the use of a double-dummy design was precluded by the absence of placebo pen devices. The questionnaires about treatment were related to the use of the device and therefore a blinded study was not possible.
Synthesis of Classical, Three-Carbon-Bridged 5-Substituted Furo[2,3-d]pyrimidine and 6-Substituted Pyrrolo[2,3-d]pyrimidine Analogues as Antifolates (2004)

Bridge homologation of the previously reported classical two-carbon-bridged antifolates, a 5-substituted 2,4-diaminofuro[2,3-d]pyrimidine (1) [which is a 6-regioisomer of LY231514 (Alimta)] and a 6-subsituted 2-amino-4-oxopyrrolo[2,3-d]pyrimidine, afforded the three-carbon-bridged antifolates analogues 4 and 5, with enhanced inhibitory activity against tumor cells in culture (EC50 values in the 10-8−10-7 M range or less). These two analogues were synthesized via a 10-step synthetic sequence starting from methyl 4-bromobenzoate (14), which was elaborated to the α-chloromethyl ketone (8) followed by condensation with 2,6-diamino-pyrimidin-4-one (7) to afford the substituted furo[2,3-d]pyrimidine 9 and the pyrrolo[2,3-d]pyrimidine 10. Subsequent coupling of each regioisomer with diethyl-l-glutamate followed by saponification afforded 4 and 5. The biological results indicate that elongation of the C8−C9 bridge of the classical 5-substituted 2,4-diaminofuro[2,3-d]pyrimidine and 6-substituted 2-amino-4-oxopyrrolo[2,3-d]pyrimidine are highly conducive to antitumor activity in vitro, despite a lack of increase in inhibitory activity against the target enzymes. This supports our original hypothesis that truncation of the B-ring of a highly potent 6−6 ring system to a 6−5 ring system can be compensated by bridge homologation to restore the overall length of the molecule.
Cancer chemoprevention: principles and prospects (1993)

Cancer chemoprevention can be defined as prevention of cancer by the administration of one or more chemical entities, either as individual drugs or as naturally occurring constituents of the diet. For several reasons, chemoprevention has received growing consideration as a means of cancer control. In the USA, the 5 year survival rate of cancer patients is currently 51 % overall (1). Among those organ sites with exceptionally low 5 year survival rates are lung (13%), ovary (39%), stomach (16%), esophagus (9%) and pancreas (3%) (1). Clearly, the considerable advances that have occurred in earlier detection and treatment of cancer have done little to improve the prognosis for patients diagnosed with cancer at certain organ sites. Thus, the aggressive prevention of cancer should be a cornerstone of any cancer control policy. Primary cancer prevention requires removal of exposure of individuals to etiologic agents. However, numerous subpopulations at high risk for certain types of cancer may already have received considerable exposure to such agents, and many human cancers cannot be ascribed to specific etiologic agents. Thus, preventative strategies that do not require prior knowledge of specific etiologic factors have great appeal. Additionally, the cost of chemopreventative programs in a given population should be considerably less than the actual health care costs incurred by any fraction of that population that develops cancer. Hence, chemoprevention of cancer may become a major weapon in the anticancer arsenal.
Efficacy of intranasal dexmedetomidine versus oral midazolam for paediatric premedication (2017)

Background and Aims: Premedication is an integral component of paediatric anaesthesia which, when optimal, allows comfortable separation of the child from the parent for induction and conduct of anaesthesia. Midazolam has been accepted as a safe and effective oral premedicant. Dexmedetomidine is a selective alpha-2 agonist with sedative and analgesic effects, which is effective through the transmucosal route. We compared the efficacy and safety of standard premedication with oral midazolam versus intranasal dexmedetomidine as premedication in children undergoing elective lower abdominal surgery. Methods: This was a prospective randomised double-blinded trial comparing the effects of premedication with 0.5 mg/kg oral midazolam versus 1 μg/kg intranasal dexmedetomidine in children between 2 and 12 years undergoing abdominal surgery. Sedation scores at separation and induction were the primary outcome measures. Behaviour scores and haemodynamic changes were secondary outcomes. Student's t-test and Chi-square were used for analysis of the variables. Results: Sedation scores were superior in Group B (dexmedetomidine) than Group A (midazolam) at separation and induction (P < 0.001). The behaviour scores at separation, induction and wake up scores at extubation were similar between the two groups. The heart rate and blood pressure showed significant differences at 15, 30 and 45 min in Group B but did not require pharmacological intervention for correction. Conclusion: Intranasal dexmedetomidine at a dose of 1 μg/kg produced superior sedation scores at separation and induction but normal behavioural scores in comparison to oral midazolam in paediatric patients.
Abstract A63: Inhibition of ROCK signaling prevents breast cancer metastasis to human bone (2009)

Abstract ROCK signaling plays a fundamental role in regulating cell morphology, adhesion and motility. Aberrant expression of ROCK is related to tumor metastases and correlates with poor clinical outcome. However, the molecular mechanisms responsible for ROCK-mediated effects and the potential utility of ROCK inhibition as a therapeutic target have not been fully investigated. Here, we show that ROCK expression is increased in metastatic human breast cancer (BrCa) cell lines and clinical mammary tumors compared to non-metastatic cell lines and tumors. Inhibition of ROCK activity, either by a specific ROCK inhibitor (Y27632) or ROCK-targeted siRNAs, reduces BrCa cell migration and proliferation in vitro. We evaluated the effect of ROCK inhibition on metastasis to bone in vivo using a novel “human BrCa metastasis to human bone” mouse model. Metastases to human bone cores (hBCs) were inhibited in Y27632-treated mice (5 out of 14, 36%) compared to control mice (8 out of 12, 67%), based on luminescent imaging. The overall frequency of metastasis to mouse skeleton in Y27632-treated mice was reduced by 36% compared to controls. Moreover, the mass of metastatic tumors in the mouse skeleton was diminished by 77% (P&amp;lt;0.05) in Y27632-treated mice. ROCK1 siRNAs also decrease the frequency of BrCa metastasis to hBCs and mouse skeleton, but to a lesser extent than Y27632. We demonstrate that ROCK's effects on tumor cell invasion/motility and growth may derive from regulating the actin-myosin cytoskeleton, modulating the c-Myc pathway by increasing the stabilization of c-Myc protein via phosphorylation, and targeting c-miRNAs. Coupled to increased c-Myc, expression of the c-Myc-regulated miR-17-92 cluster is shown here to be elevated in metastatic BrCa cells compared to non-metastatic cells, and diminished upon Y27632 treatment. Furthermore, blockade of miR-17 is shown to decrease BrCa cell invasion/migration in vitro and metastasis in vivo. Collectively, these findings suggest that augmented ROCK signaling contributes to BrCa metastasis in at least 3 ways, by 1) regulating the actin cytoskeleton and actin-myosin-dependent contractility; 2) targeting mRNAs controlled by the transcription factor c-Myc to potentiate cell growth and viability; and 3) modulating the expression of certain miRNAs, such as the c-Myc-regulated oncogenic miR-17-92 cluster. Inhibition of ROCK-mediated signaling appears to be a promising and potentially specific approach to suppress the occurrence of bone metastases in BrCa. Citation Information: Cancer Res 2009;69(23 Suppl):A63.
Altering the antigenicity of proteins. (1992)

To better understand the binding interaction between antigen and antibody we need to distinguish protein residues critical to the binding energy and mechanism from residues merely localized in the interface. By analyzing the binding of monoclonal antibodies to recombinant wild-type and mutant myohemerythrin (MHr) proteins, we were able to test the role of individual critical residues at the highly antigenic site MHr-(79-84), within the context of the folded protein. The results directly show the existence of antigenically critical residues, whose mutations significantly reduce antibody binding to the folded protein, thus verifying peptide-based assignments of these critical residues and demonstrating the ability of buried side chains to influence antigenicity. Taken together, these results (i) distinguish the antigenic surface from the solvent-exposed protein surface before binding, (ii) support a two-stage interaction mechanism allowing inducible changes in protein antigens by antibody binding, and (iii) show that protein antigenicity can be significantly reduced by alteration of single critical residues without destroying biological activity.
Reduced frequencies and suppressive function of CD4+CD25hi regulatory T cells in patients with chronic lymphocytic leukemia after therapy with fludarabine (2005)

Globally suppressed T-cell function has been described in many patients with cancer to be a major hurdle for the development of clinically efficient cancer immunotherapy. Inhibition of antitumor immune responses has been mainly linked to inhibitory factors present in cancer patients. More recently, increased frequencies of CD4+CD25hi regulatory T cells (Treg cells) have been described as an additional mechanism reducing immunity. We assessed 73 patients with B-cell chronic lymphocytic leukemia (CLL) and 42 healthy controls and demonstrated significantly increased frequencies of cytotoxic T lymphocyte-associated protein 4 (CTLA4+)-, Forkhead box P3 (FOXP3+)-, glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR+)-, CD62L+-, transforming growth factor beta1 (TGF-beta1+)-, interleukin 10 (IL-10+)-Treg cells in patients with CLL, with highest frequencies in untreated or progressing patients presenting with extended disease. Most surprisingly, in the majority of patients with CLL treated with fludarabine-containing therapy regimens the inhibitory function of Treg cells was decreased or even abrogated. In addition, frequencies of Treg cells were significantly decreased after therapy with fludarabine. In light of similar findings for cyclophosphamide the combination of fludarabine and cyclophosphamide might be further exploited in strategies reducing immunosuppression prior to cancer immunotherapy.
MPEG-7 visual shape descriptors (2001)

This paper describes techniques and tools for shape representation and matching, developed in the context of MPEG-7 standardization. The application domains for each descriptor are considered, and the contour-based shape descriptor is presented in some detail. Example applications are also shown.