gebhart/patrepeval huggingface dataset:
Targeted sequencing of refractory myeloma reveals a high incidence of mutations in CRBN and Ras pathway genes (2016)

In this study, targeted sequencing to screen 50 multidrug refractory multiple myeloma (rMM) patients was performed by using the Multiple Myeloma Mutation Panel. Patients were pretreated with both immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs), and 88%, 78%, and 68% were refractory to an IMiD, a PI, or both, respectively. The majority of patients had progressive (82%) or refractory (78%) disease immediately before sampling, with 43% being IMiD refractory and 46% being PI refractory in the most recent line of therapy. Compared with newly diagnosed MM, an increased prevalence of mutations in the Ras pathway genes KRAS, NRAS, and/or BRAF (72%), as well as TP53 (26%), CRBN (12%), and CRBN pathway genes (10%) was observed. Longitudinal analyses performed in 3 patients with CRBN mutations at time of IMiD resistance confirmed that these mutations were undetectable at earlier, IMiD-sensitive time points. Furthermore, the functional introduction of these mutations in MM cells conferred lenalidomide resistance in vitro. These data indicate a differential genetic landscape in rMM associated with drug response.
A comparison of quantitative structure-activity relationships for the effect of benzoic and cinnamic acids on Listeria monocytogenes using multiple linear regression, artificial neural network and fuzzy systems (1997)

The ability of artificial neural networks (ANN), fuzzy systems (FS) and multiple linear regression (MLR) to fit the biological activity surface describing the inhibition of Listeria monocytogenes by benzoic and cinnamic acid derivatives was compared. MLR and ANN were also compared for their ability to select the properties that best describe the biological activity of the compounds. The criteria used for comparing surface fits of all models were the coefficient of determination r2 and the standard deviation of the error, s(e). The ANN method gave a better correlation, r2 = 0.96, compared with either MLR, r2 = 0.81, or FS, r2 = 0.92, and also a lower standard error, possibly indicating non-linearity in the data. The ANN was shown to generalize better than MLR using the leave-one-out method. The ANN selection algorithm for the selection of the parameters that contributed most to the biological activity of the phenols (log K and pKa) agreed with the selected parameters of the MLR system.
Evolutionary Relationships Among Proteins Encoded by the Regulator of Complement Activation Gene Cluster (2000)

Evolutionary relationships among members of the regulator of complement activation (RCA) gene cluster were analyzed using neighbor-joining and parsimony methods of phylogenetic tree inference. We investigated the structural and functional similarities among short consensus repeats (SCRs) of the following human proteins: the alpha chain of the C4b-binding protein (C4bpalpha), factor H (FH), factor H-related proteins (FHR-1 through FHR-4), complement receptors type 1 (CR1) and type 2 (CR2), the CR1-like protein (CR1L), membrane cofactor protein (MCP), decay accelerating factor (DAF), and the sand bass proteins, the cofactor protein (SBP1) and its homolog, the cofactor-related protein (SBCRP-1). Also included are the beta chain of the human C4b-binding protein (C4bpbeta) and the b subunit of human blood-clotting factor XIII (FXIIIb). Our results indicate that the human plasma complement regulators, FH and C4bpalpha, fall into two distinct groups on the basis of their sequence divergence. Homology among RCA proteins is in agreement with their chromosomal location, with the exception of C4bpbeta. The evolutionary relationships among individual short consensus repeats are confirmed by the exon/intron structure of the RCA members. Structural similarities among repeats of the RCA proteins correlate with their functional activities and demonstrate the importance of the N-terminal SCRs.
RNAi Therapies: Drugging the Undruggable (2014)

RNA interference (RNAi) therapy is a rapidly emerging platform for personalized cancer treatment. Recent advances in small interfering RNA delivery and target selection provide unprecedented opportunities for clinical translation. Here, we discuss these advances and present strategies for making RNAi-based therapy a viable part of cancer management.
Treatment of Alzheimer's Disease by Transposition of the Omentum (2002)

There is increasing evidence that cerebral hypoperfusion plays a key role in the development of Alzheimer's disease (AD). As one ages, cerebral blood flow (CBF) decreases as a direct reflection of a normal aging process. Coupled with this expected drop in CBF are a host of other factors, such as hypertension, stress, smoking, diabetes, cholesterol buildup, etc., which further decrease blood flow to the brain. Maintaining a critical level of CBF is essential if adequate amounts of oxygen and glucose are to be presented to neurons to sustain their cellular energy production (ATP). If CBF drops below a critical flow level, insufficient ATP will be produced and, if this situation is not corrected, neurons will deteriorate and eventually die. When a critical mass of neurons die in areas of the brain involved with cognition and memory, AD will result. Omentum transposition to the brain is a surgical procedure by which a large volume of blood and other biological agents can be delivered to the brain over an indefinite period of time. The omentum gives metabolic support to deteriorating neurons and its presence on the brain has resulted in the reversal of AD symptoms. Additionally, omentum transposition to the brain can markedly reduce senile plaque accumulation, but has no apparent effect on reducing neurofibrillary tangles. Omental transposition may play an important role in the future treatment of AD, especially in early and moderate cases.
A fuzzy expert system approach to insurance risk assessment using FuzzyCLIPS (2002)

A knowledge based system (KBS) that combines fuzzy processing with rule-based expert system is developed to provide an improved decision aid for evaluating risk for life insurance. This expert system application illustrates the use of FuzzyCLIPS tool to build a knowledge based decision support system, capable of possessing fuzzy components to improve user interactions and KBS performance. The design of the fuzzy solution consists of a CLIPS rule-based system combined with fuzzy logic rules. The results employing FuzzyCLIPS are compared with the results obtained from the solution of the problem using traditional numerical equations. This paper briefly describes the problem, proposes solution, considers the test scenarios, presents the results and conclusions, and provides a sample output of the software product.
Identification of novel non‐coding RNAs as potential antisense regulators in the archaeon Sulfolobus solfataricus (2004)

By generating a specialized cDNA library from the archaeon Sulfolobus solfataricus, we have identified 57 novel small non-coding RNA (ncRNA) candidates and confirmed their expression by Northern blot analysis. The majority was found to belong to one of two classes, either antisense or antisense-box RNAs, where the latter only exhibit partial complementarity to RNA targets. The most prominent group of antisense RNAs is transcribed in the opposite orientation to the transposase genes, encoded by insertion elements (transposons). Thus, these antisense RNAs may regulate transposition of insertion elements by inhibiting expression of the transposase mRNA. Surprisingly, the class of antisense RNAs also contained RNAs complementary to tRNAs or sRNAs (small-nucleolar-like RNAs). For the antisense-box ncRNAs, the majority could be assigned to the class of C/D sRNAs, which specify 2'-O-methylation sites on rRNAs or tRNAs. Five C/D sRNAs of this group are predicted to target methylation at six sites in 13 different tRNAs, thus pointing to the widespread role of these sRNA species in tRNA modification in Archaea. Another group of antisense-box RNAs, lacking typical C/D sRNA motifs, was predicted to target the 3'-untranslated regions of certain mRNAs. Furthermore, one of the ncRNAs that does not show antisense elements is transcribed from a repeat unit of a cluster of small regularly spaced repeats in S. solfataricus which is potentially involved in replicon partitioning. In conclusion, this is the first report of stably expressed antisense RNAs in an archaeal species and it raises the prospect that antisense-based mechanisms are also used widely in Archaea to regulate gene expression.
Growth differentiation factor 15 (GDF15) promotes osteoclast differentiation and inhibits osteoblast differentiation and high serum GDF15 levels are associated with multiple myeloma bone disease (2015)

Multiple myeloma (MM) is a hematologic cancer caused by malignant plasma cells in the bone marrow. A characteristic feature of this cancer is the destruction of bone, which affects nearly all myeloma patients. The osteolytic bone disease is caused by an increased number and activity of osteoclasts, combined with a reduced number and dysfunction of osteoblasts.1
High-temperature metal coating for modification of photonic band edge position (2009)

Atomic-layer-deposited iridium is coated onto three-dimensional tungsten woodpile photonic crystals to modify the optical properties of the structure. As the lattice constant of a metallic photonic bandgap structure decreases to the scale of the near-IR wavelengths, the band edge becomes pinned and cannot be pushed to shorter wavelengths because of limitations inherent in the material. With a thin coating of iridium, the band edge of a pinned tungsten lattice is pushed from ~1.6 μm to below 1 μm. This shift in the reflectance band edge will be accompanied by a reduction in the absorptance of the structure in the 1-2 μm range.
A Mycobacterium leprae gene encoding a fibronectin binding protein is used for efficient invasion of epithelial cells and Schwann cells (1995)

Mycobacterium leprae, the causative agent of leprosy, is an obligate intracellular pathogen. M. leprae can infect a variety of cells in vivo, including epithelial cells, muscle cells, and Schwann cells, in addition to macrophages. The ligand-receptor interactions important in the attachment and ingestion of M. leprae by these nonmacrophage cells remains unknown. Fibronectin (FN) significantly enhances both attachment and ingestion of M. leprae by epithelial and Schwann cell lines. We cloned an M. leprae FN binding protein (FN attachment protein [FAP]) distinct from the 85ABC complex which has been shown previously to bind FN. The FAP open reading frame predicts a protein of 29.5 kDa with a 39-amino-acid signal peptide and was previously described as an antigen in leprosy patients. M. leprae FAP has homologies in M. vaccae, M. avium, and M. tuberculosis, as determined by Southern blotting and direct peptide analysis. Both anti-FAP antibodies and an Escherichia coli-expressed recombinant protein significantly blocked M. leprae attachment and internalization by T-24, an epithelial cell line, and JS1, a Schwann cell line. These data suggest that FN can be a bridging opsonic ligand for attachment of mycobacteria to nonphagocytes and that FAP plays an important role in this process. This may be an important step in the initiation of M. leprae infection in vivo.
Evidence for a protective role of Mcl-1 in proteasome inhibitor-induced apoptosis (2004)

Proteasome inhibitors exhibit antitumor activity against malignancies of different histology. Yet, the mechanisms underlying this effect are poorly understood. Recent evidence indicates that antiapoptotic factors may also accumulate as a consequence of exposure to these drugs, possibly reducing their cytotoxicity. These include the Bcl-2 family member Mcl-1, whose down-regulation has been proposed to initiate apoptosis in response to genotoxic stimuli. In this study, we found that proteasome inhibitors release cyotochrome c and second mitochondria-derived activator of caspase (SMAC)/Diablo and trigger the subsequent apoptotic cascade in spite of concomitant Mcl-1 increase. However, our data indicate that subtraction of Mcl-1 during apoptosis, although not required for early release of proapoptotic factors, is probably relevant in speeding up cell demise, since RNA interference-mediated Mcl-1 silencing is lethal in lymphoma cells. Consistent with this, the cytotoxic effects of proteasome inhibitors are enhanced when Mcl-1 increase is impeded. Thus, this study identifies Mcl-1 accumulation as an unwanted molecular consequence of exposure to proteasome inhibitors, which slows down their proapoptotic effects. Pharmacologic or genetic approaches targeting Mcl-1, including therapeutic RNAi, may increase the effectiveness of these compounds.
Deregulated Syk inhibits differentiation and induces growth factor–independent proliferation of pre–B cells (2006)

The nonreceptor protein spleen tyrosine kinase (Syk) is a key mediator of signal transduction in a variety of cell types, including B lymphocytes. We show that deregulated Syk activity allows growth factor-independent proliferation and transforms bone marrow-derived pre-B cells that are then able to induce leukemia in mice. Syk-transformed pre-B cells show a characteristic pattern of tyrosine phosphorylation, increased c-Myc expression, and defective differentiation. Treatment of Syk-transformed pre-B cells with a novel Syk-specific inhibitor (R406) reduces tyrosine phosphorylation and c-Myc expression. In addition, R406 treatment removes the developmental block and allows the differentiation of the Syk-transformed pre-B cells into immature B cells. Because R406 treatment also prevents the proliferation of c-Myc-transformed pre-B cells, our data indicate that endogenous Syk kinase activity may be required for the survival of pre-B cells transformed by other oncogenes. Collectively, our data suggest that Syk is a protooncogene involved in the transformation of lymphocytes, thus making Syk a potential target for the treatment of leukemia.
A single lentiviral vector platform for microRNA-based conditional RNA interference and coordinated transgene expression (2006)

RNAi is proving to be a powerful experimental tool for the functional annotation of mammalian genomes. The full potential of this technology will be realized through development of approaches permitting regulated manipulation of endogenous gene expression with coordinated reexpression of exogenous transgenes. We describe the development of a lentiviral vector platform, pSLIK (single lentivector for inducible knockdown), which permits tetracycline-regulated expression of microRNA-like short hairpin RNAs from a single viral infection of any naïve cell system. In mouse embryonic fibroblasts, the pSLIK platform was used to conditionally deplete the expression of the heterotrimeric G proteins Galpha12 and Galpha13 both singly and in combination, demonstrating the Galpha13 dependence of serum response element-mediated transcription. In RAW264.7 macrophages, regulated knockdown of Gbeta2 correlated with a reduced Ca(2+) response to C5a. Insertion of a GFP transgene upstream of the Gbeta2 microRNA-like short hairpin RNA allowed concomitant reexpression of a heterologous mRNA during tetracycline-dependent target gene knockdown, significantly enhancing the experimental applicability of the pSLIK system.
A group synchronization mechanism for live media in multicast communications (2002)

To support multicast communications for live media, the authors propose a group synchronization mechanism and enhance an intra-stream/inter-stream synchronization mechanism which they previously proposed for live media. The proposed method employs estimates of network delays for adjustment of the output timing among the destinations. The authors have implemented the mechanisms on a lip-synch experimental system. Live video of a speaker and his voice captured at a source are multicast, and then they are synchronized and output at the destinations. This paper also presents the system performance such as coefficient of variation of output interval, total pause time, mean square error of synchronization, average output rate, and average delay.
Fecal microbiota transplantation for patients with steroid-resistant acute graft-versus-host disease of the gut (2016)

Increasing evidence indicates that the gut microbiota is closely associated with acute graft-versus-host disease (aGVHD) in stem cell transplantation (SCT). Fecal microbiota transplantation (FMT) could represent an alternative treatment option for aGVHD. However, FMT for SCT patients carries a potential risk of infection by infused microbiota because of the severely immunosuppressed status. We therefore conducted a pilot study to evaluate the safety of FMT in SCT. A total of 4 patients with steroid-resistant (n = 3) or steroid-dependent gut aGVHD (n = 1) received FMT. No severe adverse events attributed to FMT were observed. All patients responded to FMT, with 3 complete responses and 1 partial response. Temporal dynamics of microbiota seemed to be linked to the gut condition of patients and peripheral effector regulatory T cells also increased during response to FMT. FMT was safely performed in our patients and might offer a novel therapeutic option for aGVHD. This trial was registered at the University Hospital Medical Information Network (https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000017575) as #UMIN000015115.
A Formal Total Synthesis of (±)-Cephalotaxine Using Sequential N-Acyliminium Ion Reactions (2002)

[reaction: see text] Novel synthesis of cephalotaxine 1 based on tertiary N-acyliminium ion chemistry starting from alkynylamide 2 was achieved. The key steps include the preparation of pyrroloisoquinoline 4 from alkynylamide 2, the ring expansion of pyrroloisoquinoline 4 to pyrrolobenzazepine 12, and the construction of cyclopentapyrrolobenzazepine ring system 6, all of which are derived from N-acyliminium ion intermediates.
Phosphorylation of Grb2-Associated Binder 2 on Serine 623 by ERK MAPK Regulates Its Association with the Phosphatase SHP-2 and Decreases STAT5 Activation (2004)

IL-2 stimulation of T lymphocytes induces the tyrosine phosphorylation and adaptor function of the insulin receptor substrate/Grb2-associated binder (Gab) family member, Gab2. In addition, Gab2 undergoes a marked decrease in its mobility in SDS-PAGE, characteristic of migration shifts induced by serine/threonine phosphorylations in many proteins. This migration shift was strongly diminished by treating cells with the MEK inhibitor U0126, indicating a possible role for ERK in Gab2 phosphorylation. Indeed, ERK phosphorylated Gab2 on a consensus phosphorylation site at serine 623, a residue located between tyrosine 614 and tyrosine 643 that are responsible for Gab2/Src homology 2 domain-containing tyrosine phosphatase (SHP)-2 interaction. We report that pretreatment of Kit 225 cells with U0126 increased Gab2/SHP-2 association and tyrosine phosphorylation of SHP-2 in response to IL-2, suggesting that ERK phosphorylation of serine 623 regulates the interaction between Gab2 and SHP-2, and consequently the activity of SHP-2. This hypothesis was confirmed by biochemical analysis of cells expressing Gab2 WT, Gab2 serine 623A or Gab2 tyrosine 614F, a mutant that cannot interact with SHP-2 in response to IL-2. Activation of the ERK pathway was indeed blocked by Gab2 tyrosine 614F and slightly increased by Gab2 serine 623A. In contrast, STAT5 activation was strongly enhanced by Gab2 tyrosine 614F, slightly reduced by Gab2 WT and strongly inhibited by Gab2 serine 623A. Analysis of the rate of proliferation of cells expressing these mutants of Gab2 demonstrated that tyrosine 614F mutation enhanced proliferation whereas serine 623A diminished it. These results demonstrate that ERK-mediated phosphorylation of Gab2 serine 623 is involved in fine tuning the proliferative response of T lymphocytes to IL-2.
The Efficacy of an Enzymic Cocktail and a Fungal Mycelium in Dephosphorylating Corn-Soybean Meal-Based Feeds Fed to Growing Turkeys (1996)

A study was conducted to determine the efficacy of phytase, an enzymic cocktail, and a waste Aspergillus niger mycelium to hydrolyze phytate present in corn-soybean meal diets. One hundred turkey poults were assigned to dietary treatments for 2 wk (days 7 to 21). Dietary treatments included: 1) NRC (1994) diet (NRC), with recommended concentration of 0.6% available P (aP) and 1.2% Ca; 2) Phytase diet (PHYT), 1,000 units phytase/kg diet, 0.16% aP, and 0.84% Ca; 3) cocktail diet (COC), 1,000 units of phytase/kg diet plus acid phosphatase (100 units/g of diet), acid protease (42 units/g of diet), pectinase (2.94%), 0.16% aP, and 0.84% Ca; 4) Fungal mycelium diet (MYC), 5% mycelium, 0.16% aP, and 0.84% Ca; and 5) a positive control diet (CTRL+), 0.42% aP, and 0.84% Ca. Turkeys fed the PHYT diet consumed less feed and gained less weight but retained more P than poults fed the CTRL+ or NRC diets. Poults fed the COC diet performed as well as poults fed CTRL+ or NRC diets but retained more P (77%) and Ca (68%). Poults fed the MYC diet retained 79% P, gained the most weight, and were more efficient than poults fed any other dietary treatment. In vitro P release from experimental diets correlated well (R = 0.906) with P retention as observed in the feeding trial. Compared with the diet containing phytase as the sole supplemental enzyme, both the enzymic cocktail and fungal mycelium enhanced performance, bone mineralization, and retention of P and Ca in growing turkeys.
Study of dual-polarized omni-directional antennas for 5.2 GHz-band 2/spl times/2 MIMO-OFDM systems (2004)

WLAN systems that use the MIMO-OFDM scheme, which enables high-speed transmission of over 100 Mbps, have been developed and are attracting much attention. The paper proposes novel dual-polarized omni-directional antennas as both the base station and personal station antennas for 5.2 GHz-band 2/spl times/2 MIMO-OFDM systems. The structure of the proposed antennas and their fundamental characteristics, such as input impedance and radiation pattern, are shown. The proposed antennas have overall dimensions of about 10 mm (diameter) and 50 mm (height) and so are very suitable for commercial use. It has been clarified that the shapes of their radiation patterns in the horizontal plane depend on their position relative to the notebook PC: the changes in radiation pattern depend mainly on the main-polarization component. Propagation measurements have been carried out in a typical office using an OFDM-MIMO channel measurement system and the channel capacities of a 2/spl times/2 OFDM-MIMO channel with the different antenna arrangements were elucidated.