gebhart/patrepeval huggingface dataset:
Small molecule inhibitors of IKK kinase activity (2005)

The nuclear transcription factor NF-κB plays a significant role in the pathogenesis of a variety of diseases. Because of the key role played by the inhibitor of κB kinase (IKK) complex in the activation of NF-κB, coupled with the druggability of kinases as a target class, numerous companies have been pursuing discovery programmes aimed at identifying small molecule inhibitors of these enzymes. This paper reviews the patenting activity associated with these efforts.
Joint optimal power control and beamforming in wireless networks using antenna arrays (1998)

The interference reduction capability of antenna arrays and the power control algorithms have been considered separately as means to increase the capacity in wireless communication networks. The minimum variance distortionless response beamformer maximizes the signal-to-interference-and-noise ratio (SINR) when it is employed in the receiver of a wireless link. In a system with omnidirectional antennas, power control algorithms are used to maximize the SINR as well. We consider a system with beamforming capabilities in the receiver, and power control. An iterative algorithm is proposed to jointly update the transmission powers and the beamformer weights so that it converges to the jointly optimal beamforming and transmission power vector. The algorithm is distributed and uses only local interference measurements. In an uplink transmission scenario, it is shown how base assignment can be incorporated in addition to beamforming and power control, such that a globally optimum solution is obtained. The network capacity and the saving in mobile power are evaluated through numerical study.
Xylanases in bleaching: From an idea to the industry (1994)

The utilization of hemicellulases in bleaching of kraft (sulphate) pulp is considered as one of the most important new large-scale industrial applications of enzymes. This is partly due to the great potential of an environmentally safe method. This method has in a short period also proven to be economically realistic. The main enzymes needed in the enzyme-aided bleaching have been shown to belong to the group of endo-/gb-xylanases. Xylanases act mainly on the relocated, reprecipitated xylan on the surface of the pulp fibres. Enzymatic hydrolysis of this specific type of xylan renders the structure of the fibres more permeable. The hydrolysis of xylan or mannan in the inner fibre layers may also enhance the bleachability. In practical process conditions, properties of the enzymes such as substrate specificity and the pH and temperature optima are of utmost importance. The benefits obtained by enzymes are dependent on the chemical bleaching sequence used as well as on the residual lignin content of pulp. The main goals in the enzyme-aided bleaching of kraft pulps have been the reduction of consumption of chlorine chemicals in the bleaching process and consequently lowering the AOX of the effluents. Enzymes have been applied as a pretreatment both in conventional (C/D)EDED and in ECF (elementary chlorine-free) bleaching sequences. In the production of TCF (totally chlorine-free) pulps, enzymes have also been successfully used for increasing the brightness of pulp.
Video object segmentation based on HOS and multi-resolution watershed (2005)

Video object extraction is a key technology in content-based video coding such as MPEG-5. An image segmentation method for extraction of video objects from a video sequence is proposed by combining the temporal segmentation result with the spatial segmentation result. HOS (higher-order statistics) are used in the temporal segmentation, and a rough motion mask is obtained through post-processing. In the spatial segmentation, the multi-resolution watershed is proposed. Segmentation only based on motion information is unlikely to achieve an accurate result without the help of spatial information. So, the video object with accurate boundaries is extracted by combining the motion mask with regions segmented by using the multi-resolution watershed. The experimental results show that the proposed algorithm improves the performance of detection of moving objects.
Cancer Statistics, 2003 (2003)

Each year, the American Cancer Society estimates the number of new cancer cases and deaths expected in the United States in the current year, and compiles the most recent data on cancer incidence, mortality, and survival by using incidence data from the National Cancer Institute (NCI) and mortality data from the National Center for Health Statistics (NCHS). Incidence and death rates are age adjusted to the 2000 US standard population. In the year 2003, we estimate that 1,334,100 new cases of cancer will be diagnosed, and 556,500 people will die from cancer in the United States. Age-adjusted cancer death rates declined in both males and females in the 1990s, though the magnitude of decline is substantially higher in males than in females. In contrast, incidence rates continued to increase in females while stabilizing in males. African-American males showed the largest decline for mortality. However, African Americans still carry the highest burden of cancer with diagnosis of cancer at a later stage and poorer survival within each stage compared with Whites. In spite of the continued decline in cancer death rates in the most recent time period, the total number of recorded cancer deaths in the United States continues to increase slightly due to the aging and expanding population.
The Fabrik programming environment (2003)

Fabrik is an experimental interactive graphical programming environment designed to simplify the programming process by integrating the user interface, the programmer language and its representation, and the environmental languages used to construct and debug programs. The programming language uses a functional, bidirectional data-flow model that trivializes syntax and eliminates the need for some traditional programming abstractions. Program synthesis is simplified by the use of aggregate and application-specific operations, modifiable examples, and the direct construction of graphical elements. The user interface includes several features designed to ease the construction and editing of the program graphs. Understanding of both individual functions and program operation are aided by immediate execution and feedback as the program is edited.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Effect of various interleukins (IL-1, IL-2, and IL-3) on the in vitro radioprotection of bone marrow progenitors (CFU-GM and CFU-MEG). (1989)

Radiation exposure to various systems can result in the development of severe toxicity, known as the acute radiation syndrome, with hematopoietic tissues being acutely susceptible to radiation-induced injury. Usually it is the degree of hematopoietic toxicity that determines the feasibility of further tumor control doses of therapy. Therefore the development of agents capable of protecting hematopoietic tissues could have important clinical applications. The cytokine interleukin-1 (IL-1) has been demonstrated to be an effective agent capable of protecting hematopoietic tissues in vivo from the toxicity associated with radiation exposure. We report here the results of studies designed to further investigate the capability of various cytokines (IL-1 and interleukins-2 and -3) to protect bone marrow-derived hematopoietic progenitors [granulocyte-macrophage and megakaryocyte colony-forming units (CFU-GM and CFU-Meg)] from radiation exposure in vitro. Only IL-1 was effective in protecting CFU-GM and CFU-Meg from radiation-induced toxicity in the range of 1-10 U/ml; however, no protection was observed when the radiation dose was greater than 300 rad. The ability of IL-1 to block radiation-induced toxicity was negated in the presence of an antibody to IL-1. These studies provide further information on the effectiveness of IL-1 in protecting in vitro hematopoietic tissues from toxicity associated with radiation exposure.
Assessing early numeracy: Significance, trends, nomenclature, context, key topics, learning framework and assessment tasks (2013)

This article describes a comprehensive and novel approach to assessment in early numeracy. Topics include the significance of early numeracy, developing a nomenclature for early numeracy, and describing the context for the development of this approach to assessment. The largely unrealised importance of numerals and numeral sequences in early numeracy, the significance of counting and its distinction from saying a number word sequence, the important topics of structuring numbers in the range 1 to 20 and conceptual place value, the Learning Framework in Number and its use in profiling children’s early numeracy knowledge, and important assessment tasks are explored.
The posttranscriptional control element of the simian retrovirus type 1 forms an extensive RNA secondary structure necessary for its function (1996)

It was previously shown that a 240-nucleotide (nt) RNA element (cis-acting transactivation element [CTE]) located between the env gene and the 3' long terminal repeat of simian retrovirus type 1 (SRV-1) can functionally replace posttranscriptional activation directed by Rev and the Rev-responsive element (RRE) when inserted into a Rev- and RRE-deficient molecular clone of human immunodeficiency virus type 1, resulting in efficient virus replication. Here, we analyze the molecular and structural requirements for function of this RNA element. Deletion mutagenesis demonstrated that the core element spans 173 nt. SRV-2 and Mason-Pfizer monkey virus have highly homologous elements, which function similarly when inserted into the Rev/RRE-deficient human immunodeficiency virus type 1. Computer prediction indicated that the core CTEs of all three viruses have similar extensive secondary structures. Mutagenesis of the SRV-1 CTE revealed that both sequence and secondary structure are essential for function. Nuclease probing of the SRV-1 CTE further supported the genetic analysis and confirmed the predicted structural features of the RNA element. Sequence analysis of the 240-nt SRV-1 CTE, after continuous long-term propagation of the Rev-independent viruses, revealed that the genetically defined core element remained unchanged, while regions outside the core CTE underwent deletions or duplications. These data further support our in vitro mutagenesis data and demonstrate the importance of the sequence and structure of the SRV-1 CTE for appropriate function.
Cytokine Signals Are Sufficient for HIV-1 Infection of Resting Human T Lymphocytes (1999)

Lentiviral vectors have been advocated to be effective vehicles for the delivery and stable expression of genes in nondividing primary cells. However, certain cell types, such as resting T lymphocytes, are resistant to infection with HIV-1. Establishing parameters for stable gene delivery into primary human lymphocytes and approaches to overcome the resistance of resting T cells to HIV infection may permit potential gene therapy applications, genetic studies of primary cells in vitro, and a better understanding of the stages of the lentiviral life cycle. Here we demonstrate that an HIV-1-derived vector can be used for stable delivery of genes into activated human T cells as well as natural killer and dendritic cells. Remarkably, a sizeable fraction of resting T cells was stably transduced with the HIV-1 vector when cultured with the cytokine interleukin (IL)-2, IL-4, IL-7, or IL-15, or, at a lower level, with IL-6, in the absence of any other stimuli. Resting T cells stimulated with these cytokines could also be infected with replication-competent HIV-1. To test the utility of this system for performing structure-function analysis in primary T cells, we introduced wild-type as well as a mutant form of murine CD28 into human T cells and showed a requirement for the CD28 cytoplasmic domain in costimulatory signaling. The ability to stably express genes of interest in primary T cells will be a valuable tool for genetic and structure-function studies that previously have been limited to transformed cell lines. In addition, the finding that cytokine signals are sufficient to permit transduction of resting T cells with HIV may be relevant for understanding mechanism of HIV-1 transmission and pathogenesis.
Transient Transfection Methods for Clinical Adeno-Associated Viral Vector Production (2009)

Recombinant adeno-associated virus (AAV)-based vectors expressing therapeutic gene products have shown great potential for human gene therapy. One major challenge for translation of promising research to clinical development is the manufacture of sufficient quantities of AAV vectors that meet stringent standards for purity, potency, and safety required for human parenteral administration. Several methods have been developed to generate recombinant AAV in cell culture, each offering distinct advantages. Transient transfection-based methods for vector production are reviewed here, with a focus on specific considerations for development of AAV vectors as clinical products.
Coordinate activation of lysosomal, Ca2+-activated and ATP-ubiquitin-dependent proteinases in the unweighted rat soleus muscle (1996)

Nine days of hindlimb suspension resulted in atrophy (55%) and loss of protein (53%) in rat soleus muscle due to a marked elevation in protein breakdown (66%, P < 0.005). To define which proteolytic system(s) contributed to this increase, soleus muscles from unweighted rats were incubated in the presence of proteolytic inhibitors. An increase in lysosomal and Ca 2+-activated proteolysis (254%, P < 0.05) occurred in the atrophying incubated muscles. In agreement with the measurements in vitro, cathepsin B, cathepsins B + L and m-calpain enzyme activities increased by 111%, 92% and 180% (P < 0.005) respectively in the atrophying muscles. Enhanced mRNA levels for these proteinases (P < 0.05 to P < 0.001) paralleled the increased enzyme activities, suggesting a transcriptional regulation of these enzymes. However, the lysosomal and Ca 2+-dependent proteolytic pathways accounted for a minor part of total proteolysis in both control (9%) and unweighted rats (18%). Furthermore the inhibition of these pathways failed to suppress increased protein breakdown in unweighted muscle. Thus a non-lysosomal Ca 2+-independent proteolytic process essentially accounted for the increased proteolysis and subsequent muscle wasting. Increased mRNA levels for ubiquitin, the 14 kDa ubiquitin-conjugating enzyme E2 (involved in the ubiquitylation of protein substrates) and the C2 and C9 subunits of the 20 S proteasome (i.e. the proteolytic core of the 26 S proteasome that degrades ubiquitin conjugates) were observed in the atrophying muscles (P < 0.02 to P < 0.001). Analysis of C9 mRNA in polyribosomes showed equal distribution into both translationally active and inactive mRNA pools, in either unweighted or control rats. These results suggest that increased ATP-ubiquitin-dependent proteolysis is most probably responsible for muscle wasting in the unweighted soleus muscle.
High-Throughput Optimization of Ir-Catalyzed C–H Borylation: A Tutorial for Practical Applications (2013)

With the aid of high-throughput screening, the efficiency of Ir-catalyzed C-H borylations has been assessed as functions of precatalyst, boron reagent, ligand, order of addition, temperature, solvent, and substrate. This study not only validated some accepted practices but also uncovered unconventional conditions that were key to substrate performance. We anticipate that insights drawn from these findings will be used to design reaction conditions for substrates whose borylations are difficult to impossible using standard catalytic conditions.
Association Between Type of Dietary Fish and Seafood Intake and the Risk of Incident Type 2 Diabetes (2009)

Total, white, and oily fish consumption may be beneficial for reducing risk of diabetes, reinforcing the public health message to consume fish regularly. Greater shellfish intake seems to be associated with an increased risk of diabetes, warranting further investigation into cooking methods and mechanisms.
Voluntary Task Switching: Chasing the Elusive Homunculus. (2005)

In the voluntary task switching procedure, subjects choose the task to perform on a series of bivalent stimuli, requiring top-down control of task switching. Experiments 1-3 contrasted voluntary task switching and explicit task cuing. Choice behavior showed small, inconsistent effects of external stimulus characteristics, supporting the assumption of top-down control of task choice. Switch costs were smaller when subjects chose to switch tasks than when instructed by an external cue. Experiments 4-6 separated choice costs from switch costs. These findings support models of task switching that incorporate top-down processes in accounts of switch costs. The degree to which task switching procedures capture top-down versus bottom-up processes may depend on the extent of environmental support provided by the procedure.
Einfache Umwandlung von 2,2′-Anhydrocytidin in 2′-Desoxy-2′-fluorcytidin durch nucleophile Substitution mit Kaliumfluorid/Kronenether (1978)

Die Fluorierung des Anhydrocytidins (1) zum Desoxyfluorcytidin (2), einer Vorstufe pharmakologisch interessanter Verbindungen, gelingt mit DMF/KF/Kronenether bei rigorosem Feuchtigkeitsausschluß. Wasserspuren überführen (1) in (3).
Abstract 3819: INCAGN02385 is an antagonist antibody targeting the co-inhibitory receptor LAG-3 for the treatment of human malignancies (2018)

Abstract Lymphocyte activation gene 3 (LAG-3) is a cell surface receptor that negatively regulates antigen-specific T cell responses. LAG-3 expression is generally restricted to populations of recently activated and chronically stimulated exhausted T cells, and is often correlated with general T cell dysfunction across several human malignancies. Accordingly, the LAG-3 pathway has been identified as a potential barrier to productive tumor-specific T cell immunity generated by PD-1/PD-L1 blockade. The antitumor activity from targeting the LAG-3 pathway in preclinical models has provided further rationale for pharmacologic modulation of the LAG-3 axis in cancer patients. INCAGN02385 is an Fc-engineered IgG1κ antibody chosen for development based on its high-affinity binding to human LAG-3, cross-reactivity with cynomolgus monkey LAG-3, and ability to potently block LAG-3 binding with its MHC class II ligand. INCAGN02385 also enhances T cell responsiveness to TCR stimulation alone or in combination with PD-1/PD-L1 axis blockade. Evaluation of INCAGN02385 in cynomolgus monkeys was well-tolerated and demonstrated the expected pharmacokinetic profile. Altogether, these data support assessment of INCAGN02385 in patients with advanced or metastatic solid tumors. Citation Format: David Savitsky, Rebecca Ward, Christina Riordan, Cornelia Mundt, Shawn Jennings, Joe Connolly, Mark Findeis, Michele Sanicola, Dennis Underwood, Horacio Nastri, Peggy Scherle, Gregory Hollis, Reid Huber, Robert Stein, Marc van Dijk, Nicholas S. Wilson. INCAGN02385 is an antagonist antibody targeting the co-inhibitory receptor LAG-3 for the treatment of human malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3819.
[Evaluation of an ultrasonic cutting and coagulating system (harmonic scalpel) for performing a segmental and wedge resection of the lung]. (1998)

In order to prevent the local recurrence of malignant tumors, it is important for surgeon to maintain a sufficient margin between the tumor and the edge at resection. For this reason we do not use an auto-suturing device, but instead use the ultrasonic cutting and coagulating system (HARMONIC SCALPEL, ETHICON ENDO-SURGERY Cincinnati, Ohio) whenever we perform either a segmental resection or a wedge resection of the lung. The subjects investigated consisted of 24 cases of lung tumors (15 metastatic tumors, 5 cases with primary lung cancer, 3 inflammatory tumors; and one benign tumor). The type of operation included 10 segmental resections and 14 wedge resections, with 21 open thoracotomies and 3 instances of thoracoscopic surgery, while 15 were single resections and 9 were multiple resections. Little bleeding was seen at the resection of the parenchyma and the vessels of the lung. However prolonged air leakage was observed in some cases that needed pleurodesis. The mean duration time of the surgery was 266 minutes, and the mean blood loss was 173 ml. The operative duration was a little longer than normal, because many cases were not first thoracotomies and some cases had multiple tumors. Nevertheless the amount of blood loss was slight. The longest post-operative period was two years and six months, no local recurrence has yet been seen in any of malignant cases. We consider this system to be very effective for performing a resection of the lung parenchyma because of the reduced blood loss and the apparent increased prevention of recurrence.
Geraniol, an Inhibitor of Mevalonate Biosynthesis, Suppresses the Growth of Hepatomas and Melanomas Transplanted to Rats and Mice (1995)

Farnesyl-pyrophosphate is required for the posttranslational modification of G proteins including p21 ras, prelamin A and lamin B, each of which plays an essential role in cell proliferation. As a consequence, competitive inhibitors of mevalonate synthesis, the rate-limiting substrate for the synthesis of the prenyl-pyrophosphates, arrest cultured cells at the G1/S interface of the cell cycle and initiate apoptotic cell death. Geraniol, an acyclic monoterpenoid alcohol, suppresses 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity and concomitantly arrests the growth of cultured tumor cells. We evaluated the impact of dietary geraniol on the growth of two tumors. In the first study, geraniol (23 mmol/kg diet, 350 mumol/d) was fed to male buffalo rats for 14 d before and for 42 d after the transplant of Morris 7777 hepatomas. Tumor growth was suppressed (P < 0.001). In the second study, the dose-dependent impact of geraniol on the growth of B16 melanomas was assessed. Dietary geraniol (0.65, 6.5 and 65 mmol/kg diet) was fed to female C57BL mice for 14 d before and for 21 d after tumor transplant. Tumor growth was suppressed (P < 0.02) by 6.5 and 65 mmol geraniol/kg diet.
Preparation of factor IX deficient human plasma by immunoaffinity chromatography using a monoclonal antibody (1982)

A murine hybridoma clone is described that grows continuously in culture and produces a monoclonal antibody we have called Royal Free Monoclonal Antibody to factor IX No. 1 (RFF-IX/1). This has high affinity for a coagulation site on factor IX. RFF-IX/1 immobilised on sepharose can be used to deplete factor IX from normal human plasma. This immunoaffinity depleted plasma is indistinguishable from severe Christmas disease plasma and can be used as the substrate in a one stage coagulation assay for factor IX. The affinity column has high capacity and can be regenerated so that large scale production from normal plasma of factor IX deficient plasma as a diagnostic reagent is now feasible.
High-speed electro-optic analogue to digital converters (2002)

Interleaved architectures can substantially increase the speed of analogue-to-digital converters (ADCs). Problems of timing jitter have limited the maximum speed of all-electronic ADCs to about 1 Gs/s. An optoelectronic solution is proposed which will remove this restriction and fully exploit the potential of the interleaved architecture. Fully integrated optically triggered sample-and-hold circuits are fabricated for the first time, using GaAs MESFET technology. Preliminary test results are presented.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>