gebhart/patrepeval huggingface dataset:
Antitumor Agents. 217. Curcumin Analogues as Novel Androgen Receptor Antagonists with Potential as Anti-Prostate Cancer Agents (2002)

A number of curcumin analogues were prepared and evaluated as potential androgen receptor antagonists against two human prostate cancer cell lines, PC-3 and DU-145, in the presence of androgen receptor (AR) and androgen receptor coactivator, ARA70. Compounds 4 [5-hydroxy-1,7-bis(3,4-dimethoxyphenyl)-1,4,6-heptatrien-3-one], 20 [5-hydroxy-1,7-bis[3-methoxy-4-(methoxycarbonylmethoxy)phenyl]-1,4,6-heptatrien-3-one], 22 [7-(4-hydroxy-3-methoxyphenyl)-4-[3-(4-hydroxy-3-methoxyphenyl)acryloyl]-5-oxohepta-4,6-dienoic acid ethyl ester], 23 [7-(4-hydroxy-3-methoxyphenyl)-4-[3-(4-hydroxy-3-methoxyphenyl)acryloyl]5-oxohepta-4,6-dienoic acid], and 39 [bis(3,4-dimethoxyphenyl)-1,3-propanedione] showed potent antiandrogenic activities and were superior to hydroxyflutamide, which is the currently available antiandrogen for the treatment of prostate cancer. Structure-activity relationship (SAR) studies indicated that the bis(3,4-dimethoxyphenyl) moieties, the conjugated beta-diketone moiety, and the intramolecular symmetry of the molecules seem to be important factors related to antiandrogenic activity. The data further suggest that the coplanarity of the beta-diketone moiety and the presence of a strong hydrogen bond donor group were also crucial for the antiandrogenic activity, which is consistent with previous SAR results for hydroxyflutamide analogues. When the pharmacophoric elements of dihydrotestosterone (DHT) and compound 4 are superposed, the resulting construct implies that the curcumin analogues may function as a 17alpha-substituted DHT. Compounds 4, 20, 22, 23, and 39 have been identified as a new class of antiandrogen agents, and these compounds or their new synthetic analogues could be developed into clinical trial candidates to control androgen receptor-mediated prostate cancer growth.
Proteolytic degradation of the RGD-binding and non-RGD-binding conformers of human platelet integrin glycoprotein IIb/IIIa: clues for identification of regions involved in the receptor's activation (1994)

The human integrin glycoprotein (GP)IIb/IIIa plays a central role in haemostasis as an inducible receptor for fibrinogen and other RGD-containing adhesive proteins at the platelet plasma membrane. Expression of the fibrinogen receptor on platelet activation involves conformational changes in the quaternary structure of GPIIb/IIIa. Little is known, however, about the nature of this conformational transition. Given that isolated GPIIb/IIIa contains a mixture of RGD-binding and non-RGD-binding heterodimers, we used limited proteolysis as a tool for investigating the structural differences between the two conformers. Comparison of their fragmentation patterns shows that, whereas in the non-RGD-binding form of GPIIb/IIIa the N-terminal half of the heavy chain of GPIIb (GPIIbH) and the central region of GPIIIa are cleaved by endoproteinase Arg-C, these domains associate tightly with one another in the RGD-binding GPIIb/IIIa and are thus protected from proteolysis. In addition, the C-terminal half of GPIIb becomes more susceptible to degradation in the non-RGD-binding GPIIb/IIIa conformer. Our interpretation, in the context of available structural and functional data, is that a major relative reorientation of the GPIIbH and GPIIIa extracellular domains takes place along the subunit interface during the conformational transition of the platelet integrin.
The long-range interaction landscape of gene promoters (2012)

The vast non-coding portion of the human genome is full of functional elements and disease-causing regulatory variants. The principles defining the relationships between these elements and distal target genes remain unknown. Promoters and distal elements can engage in looping interactions that have been implicated in gene regulation. Here we have applied chromosome conformation capture carbon copy (5C) to interrogate comprehensively interactions between transcription start sites (TSSs) and distal elements in 1% of the human genome representing the ENCODE pilot project regions. 5C maps were generated for GM12878, K562 and HeLa-S3 cells and results were integrated with data from the ENCODE consortium. In each cell line we discovered >1,000 long-range interactions between promoters and distal sites that include elements resembling enhancers, promoters and CTCF-bound sites. We observed significant correlations between gene expression, promoter-enhancer interactions and the presence of enhancer RNAs. Long-range interactions show marked asymmetry with a bias for interactions with elements located ∼120 kilobases upstream of the TSS. Long-range interactions are often not blocked by sites bound by CTCF and cohesin, indicating that many of these sites do not demarcate physically insulated gene domains. Furthermore, only ∼7% of looping interactions are with the nearest gene, indicating that genomic proximity is not a simple predictor for long-range interactions. Finally, promoters and distal elements are engaged in multiple long-range interactions to form complex networks. Our results start to place genes and regulatory elements in three-dimensional context, revealing their functional relationships.
Minimum snap trajectory generation and control for quadrotors (2011)

We address the controller design and the trajectory generation for a quadrotor maneuvering in three dimensions in a tightly constrained setting typical of indoor environments. In such settings, it is necessary to allow for significant excursions of the attitude from the hover state and small angle approximations cannot be justified for the roll and pitch. We develop an algorithm that enables the real-time generation of optimal trajectories through a sequence of 3-D positions and yaw angles, while ensuring safe passage through specified corridors and satisfying constraints on velocities, accelerations and inputs. A nonlinear controller ensures the faithful tracking of these trajectories. Experimental results illustrate the application of the method to fast motion (5-10 body lengths/second) in three-dimensional slalom courses.
Acute coronary syndromes and diabetes mellitus (2004)

Patients with diabetes mellitus who present with acute ST-segment elevation myocardial infarction or non-ST-segment elevation acute coronary syndromes have a higher risk of adverse outcomes than patients without diabetes, and appear to derive greater benefit from evidence-based therapies. However, patients with diabetes mellitus are less commonly treated with proven therapies, so renewed efforts are needed to improve the quality of care and outcomes for patients with diabetes mellitus who present with acute coronary syndromes.
First update of the International Xenotransplantation Association consensus statement on conditions for undertaking clinical trials of porcine islet products in type 1 diabetes—Chapter 6: patient selection for pilot clinical trials of islet xenotransplantation (2016)

Patients in whom type 1 diabetes is complicated by impaired awareness of hypoglycemia and recurrent episodes of severe hypoglycemia are candidates for islet or pancreas transplantation if severe hypoglycemia persists after completion of a structured stepped care approach or a formalized medical optimization run-in period that provides access to hypoglycemia-specific education including behavioral therapies, insulin analogs, and diabetes technologies under the close supervision of a specialist hypoglycemia service. Patients with type 1 diabetes and end-stage renal failure who cannot meet clinically appropriate glycemic goals or continue to experience severe hypoglycemia after completion of a formalized medical optimization program under the guidance of an expert diabetes care team are candidates for islet or pancreas transplantation either simultaneously with or after a previous kidney transplant. Similarly, patients with type 2 diabetes and problematic hypoglycemia or renal failure who meet these criteria are considered candidates for islet replacement. Likewise, patients with pancreatectomy-induced diabetes in whom an islet autograft was not available or deemed inappropriate are candidates for islet or pancreas transplantation if extreme glycemic lability persists despite best medical therapy. To justify participation of these transplant candidates in early-phase trials of porcine islet cell products, lack of timely access to islet or pancreas allotransplantation due to allosensitization, high islet dose requirements, or other factors, or alternatively, a more favorable benefit-risk determination associated with the xenoislet than the alloislet or allopancreas transplant must be demonstrated. Additionally, in non-uremic xenoislet recipients, the risks associated with diabetes must be perceived to be more serious than the risks associated with the xenoislet product and the rejection prophylaxis, and in xenoislet recipients with renal failure, the xenoislet product and immunosuppression must not impact negatively on renal transplant outcomes. The most appropriate patient group for islet xenotransplantation trials will be defined by the specific characteristics of each investigational xenoislet product and related technologies applied for preventing rejection. Selecting recipients who are more likely to experience prolonged benefits associated with the islet xenograft will help these patients comply with lifelong monitoring and other public health measures.
Expression of genes for insulin and insulin‐like growth factors and receptors in early postimplantation mouse embryos and embryonal carcinoma cells (1990)

The expression of genes for insulin and insulin-like growth factors (IGFs) and their receptors was examined in early postimplantation mouse embryos and differentiating F9 embryonal carcinoma cells using mRNA phenotyping. Messenger RNA phenotyping involves the reverse transcription of RNA followed by amplification of specific target cDNA sequences using the polymerase chain reaction (PCR). The identities of the resulting PCR fragments were confirmed using at least two of the following methods: 1) size determination by agarose gel electrophoresis, 2) the presence of diagnostic restriction sites, 3) hybridization with radiolabeled cDNA probes, 4) sequencing of the PCR fragment. Transcripts for insulin receptors, IGF-I receptors, and IGF-II receptors were detected in RNA samples from day 7.5 to day 9.5 mouse embryos and in F9 cells, although the level of insulin receptor mRNA in F9 cells was very low. Transcripts for both IGF-I and IGF-II ligands were also detectable in the embryo and F9 RNA samples, but transcripts for insulin ligand were undetectable in either set of material. The results suggest that insulin does not act as a paracrine or autocrine growth factor in early postimplantation embryos or F9 cells but that both embryos and F9 cells have the potential to respond to exogenous (e.g., maternal) sources of insulin. Both IGF-I and IGF-II could act as paracrine or autocrine growth factors, and IGF-II is the more abundant growth factor in differentiating F9 cells.
Antitumor effects of alpha-interferon and gamma-interferon on a murine renal cancer (Renca) in vitro and in vivo. (1990)

Previous studies have shown that established murine renal cancer (Renca) can be successfully treated with the investigational drug flavone acetic acid (FAA) used in combination with recombinant interleukin 2 (IL-2). Additional experiments demonstrated that the in vivo administration of FAA rapidly induced the expression of the genes, as well as the biologically active proteins, for alpha- and beta-interferons (IFNs) as well as tumor necrosis factor alpha. Both IFN-alpha and IFN-gamma have been shown to have direct antiproliferative effects against some tumors, as well as being potent immunodulators for the induction of antitumor effector cells. Thus, the present study was designed to investigate the ability of IFN-alpha and/or IFN-gamma to mediate direct antiproliferative effects against Renca in vitro as well as to cause regression of Renca in vivo. The present study confirms that RAA and/or IL-2 are inactive against Renca in vitro, further suggesting an indirect mechanism for FAA-induced antitumor effects in vivo. However, the exposure of Renca in vitro to recombinant human IFN-alpha A/D, murine IFN-alpha or murine IFN-beta resulted in a dose dependent growth inhibition of Renca as assessed by the microculture tetrazolium dye incorporation assay. Very little growth inhibition was induced by recombinant murine IFN-gamma. Interestingly, IFN-alpha (100-1000 units/ml) when combined with very low doses of recombinant murine IFN-gamma (1-10 units/ml) yielded significantly more pronounced growth inhibition than either cytokine alone. This effect was most evident by 5 days of culture where combinations of 100-1000 units/ml recombinant human IFN-alpha A/D with 1-5 units/ml recombinant murine IFN-gamma yielded growth inhibition in the range of 45-99%. In order to determine whether the mechanisms for the antitumor activity of recombinant human IFN-alpha A/D and recombinant murine IFN-gamma was due to their direct antiproliferative effects, we also studied the efficacy of these combinations against i.p. Renca in athymic mice. In contrast to the potent antitumor effects observed in euthymic mice, the combination of IFN-alpha and IFN-gamma only slightly increased mean survival times in athymic mice and no long term survivors were obtained. Subsequent studies demonstrated that most mice (77%) cured of peritoneal Renca by recombinant human IFN-alpha A/D plus recombinant murine IFN-gamma were immune to rechallenge. Therefore the combination of IFN-alpha and IFN-gamma may directly inhibit the growth of Renca, but a major effect of IFNs in vivo must be to contribute to the induction of an anti-Renca immune response.
STAT3 ser727 phosphorylation and its association with negative estrogen receptor status in breast infiltrating ductal carcinoma (2006)

Abstract Although it is known that STAT3 transcriptional activity is modulated by phosphorylation at serine residue 727, the role of STAT3 serine phosphorylation in breast cancer remains mostly unexplored. In this study, we examined the expression patterns of serine residue 727‐phosphorylated STAT3 (p‐ser727‐STAT3) in breast infiltrating ductal carcinoma tissues and nearby noncancer tissues by using immunoblotting techniques, and correlated the expression profiles with clinicopathological characteristics. A significantly elevated p‐ser727‐STAT3 expression was observed in 61.8% (42/68) of breast cancer tissues as compared to corresponding noncancer tissues ( p &lt; 0.001). Further, immunohistochemical analysis also showed an increased nuclear p‐ser727‐STAT3 staining in cancer lesions. The increased p‐ser727‐STAT3 expression in breast infiltrating ductal carcinoma tissues correlated significantly with negative estrogen receptor (ER) status, increased stage of cancer and increased tumor size ( p = 0.001, 0.024 and 0.014, individually). Intriguingly, we noticed that the expression levels of p‐ser727‐STAT3 in ER‐negative breast cancer cell lines were higher than those in ER‐positive breast cancer cell lines. In ER‐positive MCF7 cells, treatment with ERα‐specific siRNA increased, whereas treatment with anticancer drug tamoxifen decreased the expression of p‐ser727‐STAT3, phenomena not observed in ER‐negative MDA‐MB‐231 cells. In conclusion, our results suggest that p‐ser727‐STAT3 may be involved in the pathogenesis of breast cancer in an ER‐dependent manner. © 2006 Wiley‐Liss, Inc.
Space-time codes for high data rate wireless communication: performance criterion and code construction (1998)

We consider the design of channel codes for improving the data rate and/or the reliability of communications over fading channels using multiple transmit antennas. Data is encoded by a channel code and the encoded data is split into n streams that are simultaneously transmitted using n transmit antennas. The received signal at each receive antenna is a linear superposition of the n transmitted signals perturbed by noise. We derive performance criteria for designing such codes under the assumption that the fading is slow and frequency nonselective. Performance is shown to be determined by matrices constructed from pairs of distinct code sequences. The minimum rank among these matrices quantifies the diversity gain, while the minimum determinant of these matrices quantifies the coding gain. The results are then extended to fast fading channels. The design criteria are used to design trellis codes for high data rate wireless communication. The encoding/decoding complexity of these codes is comparable to trellis codes employed in practice over Gaussian channels. The codes constructed here provide the best tradeoff between data rate, diversity advantage, and trellis complexity. Simulation results are provided for 4 and 8 PSK signal sets with data rates of 2 and 3 bits/symbol, demonstrating excellent performance that is within 2-3 dB of the outage capacity for these channels using only 64 state encoders.
Efficient lipofection with cisplatin-resistant human tumor cells. (1996)

Seven of seven different cisplatin-resistant human tumor cell lines showed elevated lipofection activity as compared with their sensitive parent cells, although the degree of enhancement was not quantitatively correlated with the degree of cisplatin resistance. Enhanced transfection was seen by using the same reporter gene driven by three different promoter/enhancer sequencer or by using different reporter genes driven by the same promoter/enhancer. Cells resistant to actinomycin D, bleomycin, and nitrogen mustards were not more transfectable than the sensitive parent cells. Although the mechanism of enhanced transfection in cisplatin-resistant cells is not known, data indicated that enhanced transcription, multidrug-resistant phenotype, and methallothionein overexpression do not play a role.
Estructura de mercado turístico galego (2000)

O obxectivo deste traballo e presentar unha analise da estructura do mercado turistico en Galicia. Comezamos cun estudio dos principais efectos da actividade turistica, centrandonos no mais inmediato: o desenvolvemento do propio sector. Con este fin, efectuase unha analise da evolucion da demanda e a oferta no sector turistico e, para os anos mais recentes, desagreganse os datos, o que permite deduci-los principais trazos desta actividade en Espana, e mais concretamente en Galicia.
Speech Intelligibility in Noisy Environments with One- and Two-microphone Hearing Aids (1999)

In this study speech intelligibility in background noise was evaluated with 10 binaural hearing-aid users for hearing aids with one omnidirectional microphone and a hearing aid with a two-microphone configuration (enabling an omnidirectional as well as a directional mode). Signal-to-noise ratio (SNR) measurements were carried out for three different types of background noise (speech-weighted noise, traffic noise and restaurant noise) and two kinds of speech material (bisyllabic word lists and sentences). The average SNR improvement of the directional microphone configuration relative to the omnidirectional one was 3.4 dB for noise presented from 90 degrees azimuth. This improvement was independent of the specific type of noise and speech material, indicating that one speech-in-noise condition may yield enough relevant information in the evaluation of directional microphones and speech understanding in noise.
Determining the relative effectiveness of islanding detection methods using phase criteria and nondetection zones (2000)

Islanding of a utility-interactive photovoltaic (UIPV) system occurs if the UIPV system continues to power a section of the utility system after that section has been disconnected from the utility source. Since islanding creates hazards for personnel and equipment, UIPV systems are required to detect and prevent it. It is desirable to have a simplified method of determining which islanding detection methods (IDMs) are most effective. In this paper, a previously described method for finding the nondetection zones (NDZs) of IDMs is experimentally verified. This method is used to determine the NDZs of several common IDMs. These results indicate that, of the IDMs discussed in this paper: (1) Sandia Frequency Shift (SFS) is most effective; and (2) the worst-case loads are low-power loads that are near resonance at the line frequency and have a large capacitance and small inductance (a high value of the quality factor Q).
Mitochondrial small heat‐shock protein enhances thermotolerance in tobacco plants (2004)

To clarify the role of mitochondrial small heat-shock protein (MT-sHSP) in the heat-shock response, we introduced the tomato (Lycopersicon esculentum) MT-sHSP gene under the control of the 35S promoter into tobacco (Nicotiana tabacum), and examined the thermotolerance of the transformed plants. Irrespective of the orientation, sense or antisense, of the gene, the transgenic plants exhibited a normal morphology and growth rate in the vegetative growth stage. When 4-week-old seedlings were exposed to sudden heat stress, the sense plants which overexpress the MT-sHSP gene exhibited thermotolerance, whereas the antisense plants in which the expression of the gene is suppressed exhibited susceptibility.
The Upstart Algorithm: A Method for Constructing and Training Feedforward Neural Networks (1990)

A general method for building and training multilayer perceptrons composed of linear threshold units is proposed. A simple recursive rule is used to build the structure of the network by adding units as they are needed, while a modified perceptron algorithm is used to learn the connection strengths. Convergence to zero errors is guaranteed for any boolean classification on patterns of binary variables. Simulations suggest that this method is efficient in terms of the numbers of units constructed, and the networks it builds can generalize over patterns not in the training set.
Effects of mixing intensity on tissue-engineered cartilage (2001)

Mechanical forces regulate the structure and function of many tissues in vivo; recent results indicate that the mechanical environment can decisively influence the development of engineered tissues cultured in vitro. To investigate the effects of the hydrodynamic environment on tissue-engineered cartilage, primary bovine calf chondrocytes were seeded on fibrous polyglycolic acid meshes and cultured in spinner flasks either statically or at one of nine different turbulent mixing intensities. In medium from unmixed flasks, CO(2) accumulated and O(2) was depleted, whereas in medium from mixed flasks the concentrations of both gases approached their equilibrium values. Relative to constructs exposed to nonmixed conditions, constructs exposed to mixing contained higher fractions of collagen, synthesized and released more GAG, but contained lower fractions of GAG. Across the wide range of mixing intensities investigated, the presence or absence of mixing, but not the intensity of the mixing, was the primary determinant of the GAG and collagen content in the constructs. The all-or-none nature of these responses may provide insight into the mechanism(s) by which engineered cartilage perceives changes in its hydrodynamic environment and responds by modifying extracellular matrix production and release. 2001 John Wiley & Sons, Inc.