gebhart/patrepeval huggingface dataset:
The PIK3CA gene is mutated with high frequency in human breast cancers (2004)

The phosphatidylinositol 3-kinases (PI3Ks) are known regulators of cellular growth and proliferation. It has recently been reported that somatic mutations within the PI3K subunit p110alpha (PIK3CA) are present in human colorectal and other cancers. Here we show that thirteen of fifty-three breast cancers (25%) contain somatic mutations in PIK3CA, with the majority of mutations located in the kinase domain. These results demonstrate that PIK3CA is the most mutated oncogene in breast cancer and support a role for PIK3CA in epithelial carcinogenesis.
Drug resistance-conferring mutations in Mycobacterium tuberculosis from pulmonary tuberculosis patients in Southwest Ethiopia (2016)

A high rate of drug resistance was commonly observed among failure cases. The most frequent gene mutations associated with the resistance to INH and RIF were observed in the codon 315 of the katG gene and codon 531 of the rpoB gene, respectively. Further studies on mutations in different geographic regions using DNA sequencing techniques are warranted to improve the kit by including more specific mutation probes in the kit.
Comparison and overview of currently available neurotoxins. (2014)

Several different preparations of botulinum toxins exist worldwide, none of which are identical or interchangeable. Manufacturer recommendations on all available botulinum neurotoxins advise the use of unpreserved saline for reconstitution. Side effects are mostly mild and always self-limited. More serious complications are associated with higher doses, improper injection techniques, and occur in patients with underlying comorbidities.
Resistance of human leukemic and normal lymphocytes to drug-induced DNA cleavage and low levels of DNA topoisomerase II. (1988)

Adriamycin, amsacrine, and etoposide produce protein-associated DNA breaks in numerous cell types. However, in vitro exposure to Adriamycin (0.1-50.0 micrograms/ml) resulted in no detectable DNA cleavage in lymphocytes from patients with B-cell chronic lymphocytic leukemia (CLL) or in either B- or T-lymphocytes from normal donors. In contrast, DNA cleavage was observed in T-cells from CLL patients. Exposure to amsacrine or etoposide caused at least 50-fold less DNA cleavage in CLL and normal lymphocytes as compared to L1210 cells. These findings cannot be accounted for by differences in drug uptake. An attempt was made to explain the relative resistance of human lymphocytes to drug-induced DNA cleavage. DNA topoisomerase II, an intracellular target of tested drugs, was assayed in CLL and normal human blood lymphocytes by immunoblotting. The enzyme was detected neither in unfractionated lymphocytes nor in the enriched B- and T-cells from 28 untreated patients with CLL (Stage 0-IV) and from seven normal donors. Exponentially growing L1210 cells had approximately 7 x 10(5) enzyme copies per cell, suggesting a 100-fold higher content than that of CLL or normal lymphocytes. There were, however, detectable levels of DNA topoisomerase II in cells obtained from patients with diffuse histiocytic, nodular poorly differentiated and nodular mixed lymphomas, in Burkitt's lymphoma, acute lymphoblastic leukemia and CLL with prolymphocytic transformation. DNA topoisomerase I, a potential target for anticancer chemotherapy, was detectable in CLL and normal lymphocytes, as well as in cells of other malignancies tested. The above results may offer an explanation for the ineffectiveness of Adriamycin in the treatment of CLL. It could be suggested that low levels of DNA topoisomerase II contribute to drug resistance operating in human malignancies with a large compartment of nonproliferating cells.
The Elongin BC complex interacts with the conserved SOCS-box motif present in members of the SOCS, ras, WD-40 repeat, and ankyrin repeat families (1998)

The Elongin BC complex was identified initially as a positive regulator of RNA polymerase II (Pol II) elongation factor Elongin A and subsequently as a component of the multiprotein von Hippel-Lindau (VHL) tumor suppressor complex, in which it participates in both tumor suppression and negative regulation of hypoxia-inducible genes. Elongin B is a ubiquitin-like protein, and Elongin C is a Skp1-like protein that binds to a BC-box motif that is present in both Elongin A and VHL and is distinct from the conserved F-box motif recognized by Skp1. In this report, we demonstrate that the Elongin BC complex also binds to a functional BC box present in the SOCS box, a sequence motif identified recently in the suppressor of cytokine signaling-1 (SOCS-1) protein, as well as in a collection of additional proteins belonging to the SOCS, ras, WD-40 repeat, SPRY domain, and ankyrin repeat families. In addition, we present evidence (1) that the Elongin BC complex is a component of a multiprotein SOCS-1 complex that attenuates Jak/STAT signaling by binding to Jak2 and inhibiting Jak2 kinase, and (2) that by interacting with the SOCS box, the Elongin BC complex can increase expression of the SOCS-1 protein by inhibiting its degradation. These results suggest that Elongin BC is a multifunctional regulatory complex capable of controlling multiple pathways in the cell through interaction with a short degenerate sequence motif found in many different proteins.
Dosimetry-guided radioactive iodine treatment in patients with metastatic differentiated thyroid cancer: largest safe dose using a risk-adapted approach. (2003)

Dosimetry-guided RAI treatment allows administration of the maximum possible RAI dose to achieve the maximum therapeutic benefit. Estimation of tumor dose rates helps to determine the curative versus the palliative intent of the therapy.
Interleukin-6 increases prostate cancer cells resistance to bicalutamide via TIF2 (2009)

The standard treatment for advanced, androgen-responsive prostate cancer is androgen deprivation therapy with or without a nonsteroidal antiandrogen, such as bicalutamide. Although maximal androgen blockade exhibits favorable responses in the majority of patients, prostate cancer eventually progresses to an androgen-refractory stage. The mechanism underlying bicalutamide resistance in the course of prostate cancer progression is incompletely understood. However, interleukin-6 (IL-6) plays a critical role in the development and progression of CRPC. Herein, we explored an association between IL-6 and bicalutamide resistance. To study this, series of lower and higher passages of LNCaP cell sublines generated by long-term exposure to IL-6 were used. The cells from higher passages of LNCaP treated with IL-6 developed resistance to bicalutamide treatment compared with parental LNCaP cells. The levels of transcriptional intermediary factor 2 (TIF2) in IL-6-treated LNCaP cells were found to be significantly higher than parental LNCaP cells. Down-regulation of TIF2 expression via short hairpin RNA in IL-6-treated LNCaP cells sensitized these cells to bicalutamide treatment, whereas overexpression of TIF2 in the parental LNCaP cells increased resistance to bicalutamide. Furthermore, overexpression of IL-6 attenuated bicalutamide-mediated blockage of androgen-induced androgen receptor nuclear translocation and recruitment. These results show that overexpression of IL-6 increases the resistance of prostate cancer cells to bicalutamide via TIF2. Overexpression of IL-6 not only plays an important role in prostate cancer progression but also contributes to bicalutamide resistance. Our studies suggest that bicalutamide-IL-6-targeted adjunctive therapy may lead to a more effective intervention than bicalutamide alone.
Tomato lectin resists digestion in the mammalian alimentary canal and binds to intestinal villi without deleterious effects (1985)

Experiments were designed to investigate whether orally consumed tomato lectin could resist the digestive process and function as a lectin within the alimentary canal. Rats fed on a tomato lectin-rich diet passed faeces containing serologically detectable tomato lectin, and the lectin could be shown by immunoperoxidase staining bound to intestinal villi. Moreover, radioactivity was mainly recovered from the alimentary canal 3h after 125I-labelled tomato lectin administration with only traces in the circulation or internal organs. Radioactivity absorbed into the human circulation after consumption of 125I-labelled tomato lectin was also less than that expected for a digestable protein.
Fully human antibodies to MCAM/MUC18 inhibit tumor growth and metastasis of human melanoma. (2002)

MCAM/MUC18 expression correlates with tumor thickness and metastatic potential of human melanoma cells in nude mice. Moreover, ectopic expression of MUC18 in primary cutaneous melanoma cells leads to increased tumor growth and metastasis in vivo. Here we tested the effect of a fully human anti-MUC18 antibody, ABX-MA1, on angiogenesis, tumor growth, and metastasis. ABX-MA1 had no effect on melanoma cell proliferation rate in vitro. However, when cells of the metastatic melanoma lines A375SM and WM2664 (which express high levels of MUC18) were injected s.c. into nude mice and treated with ABX-MA1 (100 micro g, weekly, i.p. for 5 weeks), tumor growth was significantly inhibited compared with control IgG-treated mice. ABX-MA1 treatment also suppressed experimental lung metastasis of these melanoma cells. ABX-MA1 disrupted spheroid formation by melanoma cells expressing MUC18 (homotypic interaction) and the ability of these cells to attach to human vascular endothelial cells [HUVECs (MUC18 positive)] in vitro. ABX-MA1 treatment of melanoma cells in vitro significantly inhibited the promoter and collagenase activity of matrix metalloproteinase 2, resulting in decreased invasion through Matrigel-coated filters. Decreased expression of matrix metalloproteinase 2 was also observed in the implanted tumors in vivo. Moreover, because HUVECs also express MUC18, ABX-MA1 directly disrupted the tube-like formation by HUVECs in an in vitro vessel formation assay. Collectively, these results point to usefulness of ABX-MA1 as a modality to treat melanoma either alone or in combination with conventional chemotherapy or other antitumor agents.
A chemostat culture as a tool for the improvement of a recombinant E. coli strain over‐producing penicillin G acylase (2001)

The recombinant strain RE3(pKA18) of Escherichia coli constitutively overproduces penicillin G acylase (PGA) from plasmid-borne gene pga. The host strain RE3 bears the same pga gene on its chromosome, the expression of which is controlled by the natural mechanism of induction with phenylacetic acid (PA). To evaluate the maximum biosynthetic capacity for PGA, induction of the chromosomal pga by PA was studied in a culture of the recombinant strain. PGA production by batch cultures of RE3(pKA18) and RE3 showed a different response to the addition of PA to the medium: while an addition of PA induces PGA in a culture of strain RE3 as expected, in recombinant cells it lowers the specific activity of PGA and a large amount of PGA is released into the culture medium. To improve the PGA production, the strain RE3(pKA18) was cultured in a carbon-limited chemostat and subjected to selection pressure in a medium supplemented with phenylacetic acid amide (PAA). Phenylacetic acid amide served as a source of nitrogen, an inducer of PGA and a factor exerting positive selection pressure on the maintenance of the recombinant plasmid. After 130 generations of growth in the presence of the inducer, no recombinant strain with constitutive expression of the chromosomal gene pga was detected in the prevailing P(+) subpopulation in the chemostat. Shake-flask experiments with the parent recombinant strain RE3(pKA18), host strain RE3, chemostat evolvant ERE3(epKA18), the cured host ERE3 alone, and its derivative after retransformation with ancestral plasmid ERE3(pKA18) showed that inactivation of the plasmid-borne pga by a frame-shift mutation (plasmid epKA18) occurred in the plasmid-bearing subpopulation accumulated in the chemostat. Marked adaptive changes evolved in the host ERE3 during a 130 generation culture: (1) the specific growth rate of the host increased by 30% in a medium without PA, (2) the copy number of plasmids pKA18 and epKA18 in the host cultured in PA-free medium dropped by about 40%, and (3) the leakage of PGA from the cell in the presence of PA found in strain RE3(pKA18) was not observed in strain ERE3(pKA18). This new recombinant strain with modified traits was constructed by means of retransformation of the evolved host ERE3 with ancestral plasmid pKA18.
Single filters for combined image geometric manipulation and enhancement (1993)

This paper presents algorithms for simultaneous image geometric manipulation and enhancement. Single filters are developed for combined image translation, resizing, rotation, and enhancement of both single channel and multichannel/color images. Single filters have advantages for real time implementation and for minimizing artifacts produced by the sequential operations on the images. A filter structure is proposed for image sharpening, softening, blurring, and edge emphasis filtering. With the appropriate choice of the parameters, it is shown that the proposed structure can implement unsharp masking, local statistical filtering, and edge emphasis filtering. Image translation, resizing, and rotation geometric operations are combined with the structure in developing single filters. Closed form expressions are developed for real time implementation of the filters through lookup tables with different types of interpolations and for both linear and nonlinear enhancement kernels. A multichannel generalization of the algorithm is presented for simultaneous color image geometric manipulation and enhancement. Schemes are proposed for adapting the degree of enhancement based on local image information. The algorithm is applied for a number of electronic imaging applications and the evaluation results are presented.
α-Synuclein, pesticides, and Parkinson disease (2008)

Our findings suggest that SNCA REP1 genotype and herbicides have independent effects on risk of Parkinson disease, primarily in younger subjects.
Image Representations for Visual Learning (1996)

Computer vision researchers are developing new approaches to object recognition and detection that are based almost directly on images and avoid the use of intermediate three-dimensional models. Many of these techniques depend on a representation of images that induce a linear vector space structure and in principle requires dense feature correspondence. This image representation allows the use of learning techniques for the analysis of images (for computer vision) as well as for the synthesis of images (for computer graphics).
Min-cut replication in partitioned networks (1995)

Logic replication has been shown empirically to reduce pin count and partition size in partitioned networks. This paper presents the first theoretical treatment of the min-cut replication problem, which is to determine replicated logic that minimizes cut size. A polynomial time algorithm for determining min-cut replication sets for k-partitioned graphs is derived by reducing replication to the problem of finding a maximum flow. The algorithm is extended to hypergraphs and replication heuristics are proposed for the NP-hard problem with size constraints on partition components. These heuristics, which reduce the worst-case running time by a factor of O(k/sup 2/) over previous methods, are applied to designs that have been partitioned into multiple FPGA's. Experimental results demonstrate that min-cut replication provides substantial reductions in the numbers of FPGA's and pins required.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The Design and Application of a Retargetable Peephole Optimizer (1980)

Peephole optimizers improve object code by replacing certain sequences of instructions with better sequences. This paper describes PO, a peephole optimizer that uses a symbolic machine description to simulate pairs of adjacent instructions, replacing them, where possible, with an equivalent single instruction. As a result of this organization, PO is machine independent and can be described formally and concisely: when PO is finished, no instruction, and no pair of adjacent instructions, can be replaced with a cheaper single instruction that has the same effect. This thoroughness allows PO to relieve code generators of much case analysis; for example, they might produce only load/add-register sequences and rely on PO to, where possible, discard them in favor or add-memory, add-immediate, or increment instructions. Experiments indicate that naive code generators can give good code if used with PO.
Biochemistry of the algae and cyanobacteria (1988)

Part 1 Metabolism: the flexibility and variety of algal metabolism, G.E. Fogg nitrogen reserves and dynamic reservoirs in cyanobacteria, N.G.Carr uptake and utilization of nitrogen compounds, P.J.Syrett. Part 2 Biosynthesis: lipid metabolism, J.L.Harwood et al tetrapyrrole biosynthesis - the C5 pathway, A.J.Smith and L.J.Rogers. Part 3 Bio-energetics: molecular biology of photosynthetic reaction centres, A.C.Stewart light-induced proton efflux of the cyanobacterium anabaena variabilis, S.Scherer et al dark respiration in cyanobacteria, H.C.P.Matthijs and H.J.Lubberding nitrogen fixation, J.R.Gallon and A.E.Chaplin. Part 4 Regulation: calcium-mediated regulation in the cyanobacteria?, R.J.Smith thioredoxin and enzyme regulation, P.Rowell et al the responses of cyanobacteria to salt stress, R.H.Reed and W.D.P.Stewart. Part 5 Interactions: nutrient interactions in the marine environment, Anthony G.Davies algal extracellular products - antimicrobial substances, A.K.Jones cyanobacterial toxins, G.A.Codd and G.K.Poon alga-invertebrate symbiosis, A.E.Douglas. Part 6 Biotechnology: the biotechnology of microalgae and cyanobacteria, N.W.Kerby and W.D.P.Stewart seaweed biotechnology - current status and future prospects, L.V.Evans and D.M.Butler making mutants and influencing genes - the genetic exploitation of algae and cyanobacteria, R.A.Lewin.
Salivary Gland–like Tumors of the Breast Express Basal-type Immunohistochemical Markers (2012)

Adenoid cystic, mucoepidermoid, and polymorphous low-grade carcinomas of the breast express immunohistochemical markers that characterize the intrinsic basal-like subtype of breast cancer.
Effect of FK506 and cyclosporine on primary and secondary skin allograft survival in mice. (1990)

The ability of FK506 and cyclosporine to prolong mouse skin allograft survival when given alone and in combination was studied during primary and secondary responses. The drugs were efficient immunosuppressants of both types of anti-graft responses but--as reported earlier--much lower FK506 doses were required to produce those effects. Both agents synergized when administered together during primary responses but not secondary responses. This suggests that the combination treatment may be less successful in a presensitized host, a finding with potential clinical application.
Synthesis and Crystallization of Hybrid Spherical Colloids Composed of Polystyrene Cores and Silica Shells (2004)

The Stöber method has been adopted to prepare hybrid core-shell particles by coating the surfaces of monodisperse polystyrene beads with uniform silica shells. Polystyrene beads with diameters in the range of 0.1-1.0 microm have been successfully demonstrated for use with this process, and the thickness of the silica coating could be controlled in the range of 50-150 nm by adjusting the concentration of tetraethoxysilane, the deposition time, or both. The morphology and surface smoothness of the deposited silica were found to strongly depend on a number of parameters such as the surface functional groups on the polymer beads, the pH value of the medium, and the deposition time. Hollow spheres made of silica could be obtained by selectively removing the polymer cores via calcination in air at an elevated temperature or by wet etching with toluene. These core-shell colloids were also explored as building blocks to fabricate long-range ordered lattices (or colloidal crystals) that exhibited stop bands different from those assembled from spherical colloids purely made of either polystyrene or silica.
Exercise‐stimulated interleukin‐15 is controlled byAMPKand regulates skin metabolism and aging (2015)

Aging is commonly associated with a structural deterioration of skin that compromises its barrier function, healing, and susceptibility to disease. Several lines of evidence show that these changes are driven largely by impaired tissue mitochondrial metabolism. While exercise is associated with numerous health benefits, there is no evidence that it affects skin tissue or that endocrine muscle-to-skin signaling occurs. We demonstrate that endurance exercise attenuates age-associated changes to skin in humans and mice and identify exercise-induced IL-15 as a novel regulator of mitochondrial function in aging skin. We show that exercise controls IL-15 expression in part through skeletal muscle AMP-activated protein kinase (AMPK), a central regulator of metabolism, and that the elimination of muscle AMPK causes a deterioration of skin structure. Finally, we establish that daily IL-15 therapy mimics some of the anti-aging effects of exercise on muscle and skin in mice. Thus, we elucidate a mechanism by which exercise confers health benefits to skin and suggest that low-dose IL-15 therapy may prove to be a beneficial strategy to attenuate skin aging.
New multi zinc finger protein: biosynthetic design and characteristics of DNA recognition. (1997)

New six zinc finger protein DSp1 was created by connecting two Sp1 DNA binding domains. The DNA recognition characteristics of DSp1 demonstrate that (1) this multi finger protein binds eighteen contiguous base pairs of DNA sequence, (2) each zinc finger wraps around DNA major groove, and (3) two Sp1 domains have nonequivalent contribution to the DNA binding of DSp1.
Complex Actions of Sex Steroids in Adipose Tissue, the Cardiovascular System, and Brain: Insights from Basic Science and Clinical Studies (2006)

Recent publications describing the results of the Women's Health Initiative (WHI) and other studies reporting the impact of hormone therapy on aging women have spurred reexamination of the broad use of estrogens and progestins during the postmenopausal years. Here, we review the complex pharmacology of these hormones, the diverse and sometimes opposite effects that result from the use of different estrogenic and progestinic compounds, given via different delivery routes in different concentrations and treatment sequence, and to women of different ages and health status. We examine our new and growing appreciation of the role of estrogens in the immune system and the inflammatory response, and we pose the concept that estrogen's interface with this system may be at the core of some of the effects on multiple physiological systems, such as the adipose/metabolic system, the cardiovascular system, and the central nervous system. We compare and contrast clinical and basic science studies as we focus on the actions of estrogens in these systems because the untoward effects of hormone therapy reported in the WHI were not expected. The broad interpretation and publicity of the results of the WHI have resulted in a general condemnation of all hormone replacement in postmenopausal women. In fact, careful review of the extensive literature suggests that data resulting from the WHI and other recent studies should be interpreted within the narrow context of the study design. We argue that these results should encourage us to perform new studies that take advantage of a dialogue between basic scientists and clinician scientists to ensure appropriate design, incorporation of current knowledge, and proper interpretation of results. Only then will we have a better understanding of what hormonal compounds should be used in which populations of women and at what stages of menopausal/postmenopausal life.