gebhart/patrepeval huggingface dataset:
Correlation of germ-line mutations and two-hit inactivation of the WT1 gene with Wilms tumors of stromal–predominant histology (1997)

The WT1 gene, located on chromosome 11p13, is mutated in a low number of Wilms tumors (WTs). Germ-line mutations in the WT1 gene are found in patients with bilateral WT and/or associated genital tract malformations (GU). We have identified 19 hemizygous WT1 gene mutations/deletions in 64 patient samples. The histology of the tumors with mutations was stromal-predominant in 13, triphasic in 3, blastemal-predominant in 1, and unknown in 2 cases. Thirteen of 21 patients with stromal-predominant tumors had WT1 mutations and 10 of these were present in the germ line. Of the patients with germ-line alterations, six had GU and a unilateral tumor, two had a bilateral tumor and normal GU tracts, and two had a unilateral tumor and normal GU. Three mutations were tumor-specific and were found in patients with unilateral tumors without GU. These data demonstrate a correlation of WT1 mutations with stromal-predominant histology, suggesting that a germ-line mutation in WT1 predisposes to the development of tumors with this histology. Twelve mutations are nonsense mutations resulting in truncations at different positions in the WT1 protein and only two are missense mutations. Of the stromal-predominant tumors, 67% showed loss of heterozygosity, and in one tumor a different somatic mutation in addition to the germ-line mutation was identified. These data show that in a large proportion of a histopathologically distinct subset of WTs the classical two-hit inactivation model, with loss of a functional WT1 protein, is the underlying cause of tumor development.
Poly- -hydroxybutyrate (PHB) biosynthetic genes in Rhizobium meliloti 41 (1995)

Genes encoding beta-ketothiolase (phaA), acetoacetyl-CoA reductase (phaB) and PHB-synthase (phaC) from R. meliloti 41, together with a fourth gene, referred to as ORF1, presumed to be involved in PHB biosynthesis, have been cloned and sequenced. phaA, phaB and ORF1 were identified by heterologous hybridization on a cosmid library, while phaC was isolated by cloning the transposon-tagged fragment from a R. meliloti PHB- Tn5 mutant. phaA and phaB were functionally expressed in Escherichia coli while phaC was able to complement a PHB- strain of R. meliloti 41. The three genes were sufficient to direct the production of polyhydroxyalkanoate in E. coli. The homology of ORF1 with an ORF located near the PHB genes in two phototrophic bacteria suggests its involvement in PHB synthesis.
CNOP for Diffuse Aggressive Non-Hodgkin's Lymphoma: The Nebraska Lymphoma Study Group Experience (2002)

The purpose of this study was to evaluate the CNOP regimen (cyclophosphamide, mitoxantrone, vincristine, and prednisone) throughout a community based oncology network with a large number of elderly non-Hodgkin's lymphoma (NHL) patients. Three hundred and seventy-three previously untreated patients with diffuse aggressive NHL received the CNOP regimen administered through a community oncology network, the Nebraska Lymphoma Study Group (NLSG). The complete response rate was 60% with an overall response rate of 73%. The estimated 4-year event-free survival for patients <60years was 44%, compared to 38% for those >age 60 (p = 0.18). However, the 4-year estimated overall survival for patients <60 years was 62% compared to 44% for those >60 years (p < 0.001). Prognostic factors predictive for a poor event-free survival were male gender, stage III/IV disease, Karnofsky score <80, and elevated lactic dehydrogenase (LDH). The lymphoma specific cumulative death rate was 29% for patients <60 years compared with 33% for patients >60 years (p = 0.07). After failing CNOP the 4-year overall survival (OS) was 19%. The estimated 4-year OS for patients who failed CNOP and went on to receive high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplant (ASCT) was 64% for patients < age 60 and 48% for those >60 years (p = 0.23). In conclusion, CNOP chemotherapy administered to patients with diffuse aggressive NHL in a community oncology network produces similar result to that reported for other anthracycline based regimens reported in the literature. Patients >age 60 had a higher rate of failure due to causes other than lymphoma which accounted for a worse survival long-term. However, patients of all ages who failed CNOP and who were able to receive HDC and ASCT demonstrated long-term disease survival after the transplant.
Platelet membrane involvement in blood coagulation. (1983)

Intact platelets do not show procoagulant phospholipids on their exterior. These phospholipids are located at the inside leaf of the bilayer membrane. They become available by (a) disrupture of the platelets (mechanical, osmotical etc.), (b) by a mechanism specific for the platelets, that we call the membrane flip-flop. Membrane flip-flop translocates procoagulant phospholipids (mainly phosphatidylserine) in the intact platelet from the inside to the outside. Thus the intact platelet becomes procoagulant. The trigger for the flip-flop mechanism is the simultaneous presence of small amounts of collagen and thrombin. The clotting factors IXa and VIIIa bind to the procoagulant lipids to form the factor X converting enzyme and factor Xa and factor Va to form prothrombinase.
D1-like and D2-like dopamine receptors synergistically activate rotation and c-fos expression in the dopamine-depleted striatum in a rat model of Parkinson's disease (1992)

Selective agonists for D1-like and D2-like dopamine receptors can interact synergistically to enhance each other's actions on locomotion and behavior in experimental animals. Clinically, the combination of the D2 agonist bromocriptine with L-dopa (which has pronounced D1 effects) is a highly effective treatment for Parkinson's disease. The mechanisms underlying this important receptor interaction are poorly understood and are the subject of intense study in vitro. In rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal pathway, D1-selective (but not D2-selective) dopamine agonists produce a marked increase in expression of the immediate-early gene c-fos in the striatum ipsilateral to the 6-OHDA lesion. In the experiments reported here, we have used this in vivo model to explore the possibility that combinations of D1-selective and D2-selective agonists might have effects on c-fos transcription that are different from those exhibited by D1 or D2 agonists administered alone. We examined the effects of the D1-selective agonist SKF-38393 and the D2-selective agonist quinpirole (LY 171555) on the expression of Fos-like protein and c-fos mRNA in the caudoputamen and made parallel behavioral observations in the same animals. A low dose of SKF-38393 produced little contraversive rotation and little induction of Fos-like immunoreactivity in the striatum. A low dose of quinpirole elicited contralateral rotation but little or no induction of Fos-like immunoreactivity in the caudoputamen; there was, however, induction of Fos in the globus pallidus ipsilateral to the 6-OHDA lesion. Combination of the low dose of SKF-38393 and quinpirole produced a synergistic effect on rotation and elicited, in the dopamine-depleted caudoputamen, a striking pattern of Fos-like protein expression in which Fos-positive neurons were concentrated in striosomes and in the dorsolateral caudoputamen. Northern blot analysis showed that c-fos mRNA was expressed following combined agonist treatment but was not detectable after the single-agonist treatments. Both the contraversive rotation and the induction of Fos-like immunoreactivity were blocked by the preadministration of the D1-preferring antagonist SCH-23390 and the D2-selective antagonist raclopride in combination. Pretreatment with the glutamate NMDA receptor antagonist MK-801 also blocked the induction of Fos-like immunoreactivity, and it reversed the rotation. These findings suggest a D1/D2 synergistic mechanism that involves the participation of D1-responsive striatonigral and D2-responsive striatopallidal output pathways, and that is sensitive to glutamatergic modulation.
Identification of Mycobacterium avium Genes That Affect Invasion of the Intestinal Epithelium (2005)

Invasion of intestinal mucosa of the host by Mycobacterium avium is a critical step in pathogenesis and likely involves several different bacterial proteins, lipids, glycoproteins, and/or glycolipids. Through the screening of an M. avium genomic library in Mycobacterium smegmatis, we have identified a number of M. avium genes that are associated with increased invasion of mucosal epithelial cells. In order to further investigate these genes, we cloned six of them into a plasmid downstream of a strong mycobacterial promoter (L5 mycobacterial phage promoter), resulting in constitutive expression. Bacteria were then evaluated for increased expression and examined for invasion of HT-29 intestinal epithelial cells. The genes identified encode proteins that are similar to (i) M. tuberculosis coenzyme A carboxylase, (ii) M. tuberculosis membrane proteins of unknown function, (iii) M. tuberculosis FadE20, (iv) a Mycobacterium paratuberculosis surface protein, and (v) M. tuberculosis cyclopropane fatty acyl-phopholipid synthase. The constitutive expression of these genes confers to M. avium the ability to invade HT-29 intestinal epithelial cells with a severalfold increase in efficiency compared to both the wild-type M. avium and M. avium containing the vector alone. Using the murine intestinal ligated loop model, it was observed that the constitutive expression of M. avium proteins has a modest impact on the ability to enter the intestinal mucosa when compared with the wild-type control, suggesting that under in vivo conditions these genes are expressed at higher levels. Evaluation of the expression of these invasion-related genes indicated that under conditions similar to the intestinal lumen environment, the genes identified are upregulated. These data suggest that invasion of the intestinal mucosa is an event that requires the participation of several bacterial factors and the expression of the genes that encode them is less observed under standard laboratory growth conditions.
Cloning of a cDNA for a major human protein-tyrosine-phosphatase. (1990)

We have isolated a cDNA clone encoding the major protein-tyrosine-phosphatase (protein-tyrosine-phosphate phosphohydrolase, EC 3.1.3.48) of human placenta. Degenerate oligonucleotides, based on the amino acid sequence of the protein, were used to amplify an internal fragment of the gene from human placental cDNA by the polymerase chain reaction. This fragment was then used to probe a human placental cDNA library. A 3.3-kilobase (kb) insert was isolated and sequenced. The insert has a single extended open reading frame that predicts a 435 amino acid protein of Mr approximately 50,000. From the amino terminus to residue 321, the deduced amino acid sequence is identical to that previously determined by peptide sequencing [Charbonneau, H., Tonks, N. K., Kumar, S., Diltz, C. D., Harrylock, M., Cool, D. E., Krebs, E. G., Fischer, E. H. & Walsh, K. A. (1989) Proc. Natl. Acad. Sci. USA 86, 5252-5256]; however, the sequence predicts that the protein contains an additional 114 amino acids not present in the reported peptide sequence. In vitro translation of the 3.3-kb insert produces a protein of Mr 56,000, in general agreement with the predicted size. The phosphatase gene appears to be present as a single copy in human genomic DNA and is transcribed into a 3.5-kb message in a variety of tissues.
Positional Cloning and Sequence Analysis of the Drosophila Clock Gene, timeless (1995)

The Drosophila genes timeless (tim) and period (per) interact, and both are required for production of circadian rhythms. Here the positional cloning and sequencing of tim are reported. The tim gene encodes a previously uncharacterized protein of 1389 amino acids, and possibly another protein of 1122 amino acids. The arrhythmic mutation tim01 is a 64-base pair deletion that truncates TIM to 749 amino acids. Absence of sequence similarity to the PER dimerization motif (PAS) indicates that direct interaction between PER and TIM would require a heterotypic protein association.
Clinical Features and Outcome of Patients With Non–Small-Cell Lung Cancer Harboring BRAF Mutations (2011)

Purpose To investigate the prevalence, distribution, and prognostic role of BRAF mutations in a large cohort of white patients with non–small-cell lung cancer (NSCLC). Patients and Methods A retrospective series of 1,046 NSCLCs—comprising 739 adenocarcinomas (ADCs) and 307 squamous cell carcinomas (SCCs)—was investigated for BRAF mutations. High-resolution melting analysis followed by sequencing and strip hybridization assay were used. All patients were also analyzed for KRAS and EGFR mutations. Results BRAF mutations were present in 36 ADCs (4.9%) and one SCC (0.3%; P = .001). Twenty-one of the mutations (56.8%) were V600E, and 16 (43.2%) were non-V600E. V600E mutations were significantly more prevalent in females (16 of 187 patients; 8.6%) than in males (five of 552 patients; 0.9%), as indicated by multivariate logistic regression analysis (hazard ratio [HR], 11.29; P &lt; .001). V600E-mutated tumors showed an aggressive histotype characterized by micropapillary features in 80% of patients and were significantly associated with shorter disease-free and overall survival rates on both univariate (HR, 2.67; P &lt; .001 and HR, 2.97; P &lt; .001, respectively) and multivariate analyses (HR, 2.19; P = .011 and HR, 2.18; P = .014, respectively). All non-V600E mutations were found in smokers (P = .015) and were associated with neither clinicopathologic parameters nor prognosis. BRAF and EGFR were concomitantly mutated in two tumors. Conclusion We report for the first time to our knowledge that V600E and non-V600E BRAF mutations affect different patients with NSCLC. V600E mutations are significantly associated with female sex and represent a negative prognostic factor. In addition, we identified a number of other clinicopathologic parameters potentially useful for the selection of patients carrying BRAF mutations.
Can we hit the snooze button on aging? (2017)

Wander down a supplement aisle at your local pharmacy or hop on the internet, and it’s not hard to find products that promise to “slow the normal signs of aging” or that offer “long-term well-being at the cellular level.” Humans have been trying to outsmart the inevitable for centuries. The alchemists began their search for an elixir for eternal youth some 800 years ago, when they tried to make the philosophers’ stone by converting base metals into gold.Most modern-day antiaging remedies have remarkable parallels to their alchemical predecessors: Both can yield a fast buck, but neither is based on science proven to work in humans. After hundreds of years of effort, there is still no miracle pill that can turn back time, despite the claims of zealous entrepreneurs. Some pseudoaging treatments over the years have been risky, capable of doing more harm than good—for example, injections of human growth factor
Growth modulation of mouse keratinocytes by transforming growth factors. (1988)

The effects of exogenously added transforming growth factor (TGF alpha and TGF beta on the growth of BALB/MK cells were examined. TGF alpha supplanted the epidermal growth factor (EGF) requirement in these cells. In contrast, TGF beta reversibly inhibited the growth of BALB/MK cells by abrogating the stimulatory actions of EGF or TGF alpha. The inhibitory effects of TGF beta appeared to be mediated by events distal to EGF ligand-receptor interactions. Growth inhibition of BALB/MK cells by TGF beta did not result in the induction of differentiation. This finding is different from the growth inhibition of these cells induced by elevated calcium levels (1.5 mM) which was tightly coupled to terminal differentiation. The BALB/MK cells were found to express TGF alpha mRNA, as well as TGF beta mRNA and protein. In addition, TGF alpha, as well as EGF, enhanced TGF alpha gene expression. These studies suggest a role for endogenous TGFs in regulating BALB/MK proliferation. TGF alpha provides a positive growth signal, while TGF beta is a potent inhibitor of growth even in the presence of such positive modulators as TGF alpha and EGF.
High-brightness wavelength-beam-combined diode laser stacks using a volume Bragg grating (VBG) (2006)

Using VBG-stabilized wavelength beam combining of 3-bar diode laser stack, we demonstrate 89.5 W CW with beam quality M <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> ~ 26 in the slow-axis and M <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> ~21 in the fast-axis. The beam combining efficiency is 75%.
Expression and significance of RASL11 B in clear-cell renal cell carcinoma (2014)

Objectives To investigate the expression and clinical values of RAS-like,family 11,member B (RASL11 B) in clear cell renal cell carcinoma (ccRCC).Methods Tumor tissues and adjacent non-cancerous kidney tissues were collected from 78 ccRCC undergoing nephrectomy.The expression level of RASL11B mRNA in ccRCC was measured by Quantitative Real-Time PCR.Western blot and immunohistochemistry were used to determine the expression and localizaiton of RASL11B in ccRCC and corresponding normal tissues.Results The expression level of RASL11B mRNA was significantly decreased in ccRCC tumor tissues compared with adjacent non -cancerous kidney tissues (P ＜ 0.001) ; Low RASL11 B mRNA was significantly associated with tumor clinicopathological parameters,including tumor diameter,pT stage,Fuhrman tumor grade,TNM stage grouping and macrovascular infiltration(MAVI).RASL11 B protein signals were mainly localized in the cytoplasm of normal renal tubule epithelial cells.Lower RASL11B protein expression was consistent to the trend by PCR.Conclusions The expression of RASL11B was significantly decreased in the clear cell renal cell carcinoma tissues compared to the adjacent non-cancerous tissues,which suggests that RASL11B play an important role in ccRCC.

Key words: 
Kidney Neoplasms ;  Genes;  Immunohistochemistry
Characterization and purification of a primitive hematopoietic cell type in adult mouse marrow capable of lymphomyeloid differentiation in long-term marrow "switch" cultures (1995)

In this report, we describe a modification of the assay for long-term culture-initiating cells (LTC-IC) that allows a subset of murine LTC-IC (designated as LTC-ICML) to express both their myeloid (M) and lymphoid (L) differentiative potentials in vitro. The modified assay involves culturing test cells at limiting dilutions on irradiated mouse marrow feeder layers for an initial 4 weeks under conditions that support myelopoiesis and then for an additional week under conditions permissive for B-lymphopoiesis. All of the clonogenic pre-B progenitors (colony-forming unit [CFU] pre-B) detected in such postswitch LTC appear to be the progeny of uncommitted cells present in the original cell suspension because exposure of lymphoid-restricted progenitors to myeloid LTC conditions for > or = 7 days was found to irreversibly terminate CFU-pre-B production and, in cultures initiated with limiting numbers of input cells (no progenitors of any type detected in > 70% of cultures 1 week after the switch), the presence of CFU-pre-B was tightly associated with the presence of myeloid clonogenic cells, regardless of the purity of the input population. Limiting dilution analysis of the proportion of negative cultures measured for different numbers of input cells showed the frequency of LTC-ICML in normal adult mouse marrow to be 1 per 5 x 10(5) cells with an enrichment of approximately 500-fold in the Sca-1+ Lin-WGA+ fraction, as was also found for competitive in vivo repopulating units (CRU) and conventionally defined LTC-IC. LTC-ICML also exhibited the same resistance to treatment in vivo with 5-fluorouracil (5-FU) as CRU and LTC-IC, thereby distinguishing these three populations from the great majority of both in vitro clonogenic cells and day 12 CFU-S. The ability to quantitate cells with dual lymphoid and myeloid differentiation potentials in vitro, without the need for their prior purification, should facilitate studies of totipotent hematopoietic stem cell regulation.
Remotely Triggered Liposome Release by Near-Infrared Light Absorption via Hollow Gold Nanoshells (2008)

An elusive goal for systemic drug delivery is to provide both spatial and temporal control of drug release. Liposomes have been evaluated as drug delivery vehicles for decades, but their clinical significance has been limited by slow release or poor availability of the encapsulated drug. Here we show that near-complete liposome release can be initiated within seconds by irradiating hollow gold nanoshells (HGNs) with a near-infrared (NIR) pulsed laser. Our findings reveal that different coupling methods such as having the HGNs tethered to, encapsulated within, or suspended freely outside the liposomes, all triggered liposome release but with different levels of efficiency. For the underlying content release mechanism, our experiments suggest that the microbubble formation and collapse due to the rapid temperature increase of the HGN is responsible for liposome disruption, as evidenced by the formation of solid gold particles after the NIR irradiation and the coincidence of a laser power threshold for both triggered release and pressure fluctuations in the solution associated with cavitation. These effects are similar to those induced by ultrasound and our approach is conceptually analogous to the use of optically triggered nano-"sonicators" deep inside the body for drug delivery. We expect HGNs can be coupled with any nanocarriers to promote spatially and temporally controlled drug release. In addition, the capability of external HGNs to permeabilize lipid membranes can facilitate the cellular uptake of macromolecules including proteins and DNA and allow for promising applications in gene therapy.
Safety and effectiveness of leflunomide in the treatment of patients with active rheumatoid arthritis (1995)

Leflunomide is effective in daily doses of 10 mg and 25 mg in patients with active RA. Improved efficacy at the 25-mg dose was associated with a higher incidence of AEs. Randomized, placebo-controlled trials using daily doses of 10 mg and 20 mg are under way in the US and Europe to confirm these positive results.
Depth Map Prediction from a Single Image using a Multi-Scale Deep Network (2014)

Predicting depth is an essential component in understanding the 3D geometry of a scene. While for stereo images local correspondence suffices for estimation, finding depth relations from a single image is less straightforward, requiring in-tegration of both global and local information from various cues. Moreover, the task is inherently ambiguous, with a large source of uncertainty coming from the overall scale. In this paper, we present a new method that addresses this task by employing two deep network stacks: one that makes a coarse global prediction based on the entire image, and another that refines this prediction locally. We also apply a scale-invariant error to help measure depth relations rather than scale. By leveraging the raw datasets as large sources of training data, our method achieves state-of-the-art results on both NYU Depth and KITTI, and matches detailed depth boundaries without the need for superpixelation. 1
New Communesin Derivatives from the Fungus Penicillium sp. Derived from the Mediterranean Sponge Axinella verrucosa (2003)

The ethyl acetate extract of Penicillium sp., derived from the Mediterranean sponge Axinella verrucosa, yielded the known compound communesin B (1) and its new congeners communesins C (2) and D (3), as well as the known compounds griseofulvin, dechlorogriseofulvin, and oxaline. All structures were unambiguously established by 1D and 2D NMR and MS data. In several bioassays performed on different leukemia cell lines, the communesins exhibited moderate antiproliferative activity.