gebhart/patrepeval huggingface dataset:
Pulmonary gas exchange during exercise in women: effects of exercise type and work increment (2000)

Exercise-induced arterial hypoxemia (EIAH) has been reported in male athletes, particularly during fast-increment treadmill exercise protocols. Recent reports suggest a higher incidence in women. We hypothesized that 1-min incremental (fast) running (R) protocols would result in a lower arterial PO(2) (Pa(O(2))) than 5-min increment protocols (slow) or cycling exercise (C) and that women would experience greater EIAH than previously reported for men. Arterial blood gases, cardiac output, and metabolic data were obtained in 17 active women [mean maximal O(2) uptake (VO(2 max)) = 51 ml. kg(-1). min(-1)]. They were studied in random order (C or R), with a fast VO(2 max) protocol. After recovery, the women performed 5 min of exercise at 30, 60, and 90% of VO(2 max) (slow). One week later, the other exercise mode (R or C) was similarly studied. There were no significant differences in VO(2 max) between R and C. Pulmonary gas exchange was similar at rest, 30%, and 60% of VO(2 max). At 90% of VO(2 max), Pa(O(2)) was lower during R (mean +/- SE = 94 +/- 2 Torr) than during C (105 +/- 2 Torr, P < 0.0001), as was ventilation (85.2 +/- 3.8 vs. 98.2 +/- 4.4 l/min BTPS, P < 0.0001) and cardiac output (19.1 +/- 0.6 vs. 21.1 +/- 1.0 l/min, P < 0.001). Arterial PCO(2) (32.0 +/- 0.5 vs. 30.0 +/- 0.6 Torr, P < 0.001) and alveolar-arterial O(2) difference (A-aDO(2); 22 +/- 2 vs. 16 +/- 2 Torr, P < 0.0001) were greater during R. Pa(O(2)) and A-aDO(2) were similar between slow and fast. Nadir Pa(O(2)) was </=80 Torr in four women (24%) but only during fast-R. In all subjects, Pa(O(2)) at VO(2 max) was greater than the lower 95% prediction limit calculated from available data in men (n = 72 C and 38 R) for both R and C. These data suggest intrinsic differences in gas exchange between R and C, due to differences in ventilation and also efficiency of gas exchange. The Pa(O(2)) responses to R and C exercise in our 17 subjects do not differ significantly from those previously observed in men.
Treatment of glioblastoma multiforme using a combination of small interfering RNA targeting epidermal growth factor receptor and β‐catenin (2013)

Simultaneous inhibition of EGFR and β-catenin expression could represent an effective therapy for human GBM, and warrants further study in vivo.
Encoded combinatorial chemistry: Synthesis and screening of a library of highly functionalized pyrrolidines (1997)

The application of a new encoding technology for drug discovery is described. A combinatorial library of mercaptoacyl pyrrolidines has been prepared on a beaded polymeric support. Each polymer bead carries one library constituent in association with an oligomeric "tag," the structure of which is a record of the specific reagents from which that library member was prepared. After the ligands were solubilized, an array of such beads was screened for angiotensin-converting enzyme inhibitory activity, and the structures of active pyrrolidines were deduced by analysis of the associated tags at sub-picomole levels. Several extremely potent enzyme inhibitors were identified, many from multiple beads. The most potent inhibitor was found to have a Ki of 160 pM, approximately 3-fold more active than captopril in the same assay. Direct comparison with iterative deconvolution shows that the encoded screening strategy is a much more efficient means for extracting information from such compound collections, producing more data on a larger number of active structures.
NAPOLI-3: An open-label, randomized, phase III study of first-line liposomal irinotecan + 5-fluorouracil/leucovorin + oxaliplatin versus nab-paclitaxel + gemcitabine in patients with metastatic pancreatic ductal adenocarcinoma. (2020)

TPS4661 Background: Liposomal irinotecan administered with 5-fluorouracil/leucovorin (5-FU/LV) is approved in the USA for metastatic pancreatic ductal adenocarcinoma (mPDAC) following progression with gemcitabine-based therapy. A phase 1/2 study in previously untreated locally advanced/metastatic PDAC showed promising anti-tumor activity with liposomal irinotecan 50 mg/m 2 free base + 5-FU 2400 mg/m 2 + LV 400 mg/m 2 + oxaliplatin (OX) 60 mg/m 2 on days 1 and 15 of a 28-day cycle (Wainberg et al. Ann Oncol 2019;30 Suppl 4: SO-005). Herein, we present the design of the phase 3 NAPOLI-3 study investigating the efficacy and safety of this regimen as first-line therapy in patients with mPDAC. Methods: NAPOLI-3 (NCT04083235) is a phase 3, open-label, randomized, global study in adults with histologically/cytologically confirmed pancreatic adenocarcinoma not previously treated in the metastatic setting. Patients are required to have one or more metastatic tumors measurable with computed tomography/magnetic resonance imaging and an Eastern Cooperative Oncology Group performance status score of 0–1. Site activation began in Dec 2019 and enrollment is ongoing. Random allocation (1:1) of 750 patients is planned to liposomal irinotecan + 5-FU/LV + OX (regimen as per phase 1/2 study) or nab-paclitaxel 125 mg/m 2 + gemcitabine 1000 mg/m 2 on days 1, 8 and 15 in a 28-day cycle. The primary endpoint is overall survival (OS). Secondary endpoints (progression-free survival [PFS] and overall response rate assessed with Response Evaluation Criteria in Solid Tumors v1.1 criteria) will be compared only if the primary endpoint shows superiority for liposomal irinotecan + 5-FU/ LV + OX over nab-paclitaxel + gemcitabine. Safety assessments include adverse-event monitoring. Patients will continue treatment until disease progression, unacceptable toxicity or study withdrawal, and will then be followed for survival every 2 months until death or study end (when all patients have died, withdrawn consent or are lost to follow-up). Clinical trial information: NCT04083235 .
Evaluation of left ventricular function using 99mTc-diethylenetriaminepentaacetic acid-human serum albumin (DTPA-HSA). (1988)

A newly developed blood pool agent 99mTc-DTPA-HSA (Japan Mediphysics, Inc.) was used for ECG gated blood pool scintigraphy. The radiopharmaceutical remained in the blood pool with disappearance half time of 420 min in a healthy subject. The gated blood pool study in the same subject clearly demonstrated contracting left ventricle and right ventricle both with planar and SPECT images. Three healthy volunteers and 14 patients were included in the study, in that gated blood pool images were successfully obtained. The left ventricular ejection fraction (LVEF) calculated by the analysis of LV volume curves correlated well with those obtained by echocardiography (US). In 11 patients with implanted pacemaker for complete atrioventricular block and sick sinus syndrome changes of LVEF were evaluated in relation to pacing rates. The mean LVEF at pacing rate of 60/min was 58.5%, which decreased to 54.4% at 100/min pacing rate. However, changes of LVEF in individual patient did not show same pattern. We conclude that 99mTc-DTPA-HSA is a convenient blood pool scanning agent which does not require time consuming labeling preparations. Stable labeling and slow blood clearance allows its use for repeat measurements of LVEF in different conditions in a patient such as with pacemaker.
Efficient multi-layer coding and encryption of MPEG video streams (2002)

This paper introduces a novel, light-weight video encryption algorithm that supports light-weight, multi-layered encryption. The objectives of this encryption algorithm are to reduce the total amount of data encrypted (while providing reasonable privacy and security) and to allow for the playback of the encrypted stream in the presence of network packet loss and bit-errors. The latter property allows for the easy adaptation of encrypted video over best-effort networks, such as the Internet. This algorithm partitions the stream into three layers and provides encryption on the lower two layers. An adaptive algorithm is provided that shows how to adaptively partition the video data so that the user can ensure a maximum peak signal to noise ratio in the base layer. Our results show that we can provide security by encrypting only a fraction of the data depending on the level of security the user requires.
Silencing of the HER2/neu Gene by siRNA Inhibits Proliferation and Induces Apoptosis in HER2/neu-Overexpressing Breast Cancer Cells (2004)

In eukaryotes, double-stranded (ds) RNA induces sequence-specific inhibition of gene expression referred to as RNA interference (RNAi). We exploited RNAi to define the role of HER2/neu in the neoplastic proliferation of human breast cancer cells. We transfected SK-BR-3, BT-474, MCF-7, and MDA-MB-468 breast cancer cells with short interfering RNA (siRNA) targeted against human HER2/neu and analyzed the specific inhibition of HER2/neu expression by Northern and Western blots. Transfection with HER2/neu-specific siRNA resulted in a sequence-specific decrease in HER2/neu mRNA and protein levels. Moreover, transfection with HER2/neu siRNA caused cell cycle arrest at G0/G1 in the breast cancer cell lines SK-BR-3 and BT-474, consistent with a powerful RNA silencing effect. siRNA treatment resulted in an antiproliferative and apoptotic response in cells overexpressing HER2/neu, but had no influence in cells with almost no expression of HER2/neu proteins like MDA-MB-468 cells. These data indicate that HER2/neu function is essential for the proliferation of HER2/neu-overexpressing breast cancer cells. Our observations suggest that siRNA targeted against human HER2/neu may be valuable tools as antiproliferative agents that display activity against neoplastic cells at very low doses.
Substrate Specificities of SR Proteins in Constitutive Splicing Are Determined by Their RNA Recognition Motifs and Composite Pre-mRNA Exonic Elements (1999)

We report striking differences in the substrate specificities of two human SR proteins, SF2/ASF and SC35, in constitutive splicing. β-Globin pre-mRNA (exons 1 and 2) is spliced indiscriminately with either SR protein. Human immunodeficiency virus tatpre-mRNA (exons 2 and 3) and immunoglobulin μ-chain (IgM) pre-mRNA (exons C3 and C4) are preferentially spliced with SF2/ASF and SC35, respectively. Using in vitro splicing with mutated or chimeric derivatives of the tat and IgM pre-mRNAs, we defined specific combinations of segments in the downstream exons, which mediate either positive or negative effects to confer SR protein specificity. A series of recombinant chimeric proteins consisting of domains of SF2/ASF and SC35 in various combinations was used to localize trans-acting domains responsible for substrate specificity. The RS domains of SF2/ASF and SC35 can be exchanged without effect on substrate specificity. The RNA recognition motifs (RRMs) of SF2/ASF are active only in the context of a two-RRM structure, and RRM2 has a dominant role in substrate specificity. In contrast, the single RRM of SC35 can function alone, but its substrate specificity can be influenced by the presence of an additional RRM. The RRMs behave as modules that, when present in different combinations, can have positive, neutral, or negative effects on splicing, depending upon the specific substrate. We conclude that SR protein-specific recognition of specific positive and negative pre-mRNA exonic elements via one or more RRMs is a crucial determinant of the substrate specificity of SR proteins in constitutive splicing.
Creating and exploring a large photorealistic virtual space (2008)

We present a system for exploring large collections of photos in a virtual 3D space. Our system does not assume the photographs are of a single real 3D location, nor that they were taken at the same time. Instead, we organize the photos in themes, such as city streets or skylines, and let users navigate within each theme using intuitive 3D controls that include move left/right, zoom and rotate. Themes allow us to maintain a coherent semantic meaning of the tour, while visual similarity allows us to create a ldquobeing thererdquo impression, as if the images were of a particular location. We present results on a collection of several million images downloaded from Flickr and broken into themes that consist of a few hundred thousand images each. A byproduct of our system is the ability to construct extremely long panoramas, as well as image taxi, a program that generates a virtual tour between a user supplied start and finish images. The system, and its underlying technology can be used in a variety of applications such as games, movies and online virtual 3D spaces like Second Life.
Kinome-wide Selectivity Profiling of ATP-competitive Mammalian Target of Rapamycin (mTOR) Inhibitors and Characterization of Their Binding Kinetics (2012)

An intensive recent effort to develop ATP-competitive mTOR inhibitors has resulted in several potent and selective molecules such as Torin1, PP242, KU63794, and WYE354. These inhibitors are being widely used as pharmacological probes of mTOR-dependent biology. To determine the potency and specificity of these agents, we have undertaken a systematic kinome-wide effort to profile their selectivity and potency using chemical proteomics and assays for enzymatic activity, protein binding, and disruption of cellular signaling. Enzymatic and cellular assays revealed that all four compounds are potent inhibitors of mTORC1 and mTORC2, with Torin1 exhibiting ∼20-fold greater potency for inhibition of Thr-389 phosphorylation on S6 kinases (EC(50) = 2 nM) relative to other inhibitors. In vitro biochemical profiling at 10 μM revealed binding of PP242 to numerous kinases, although WYE354 and KU63794 bound only to p38 kinases and PI3K isoforms and Torin1 to ataxia telangiectasia mutated, ATM and Rad3-related protein, and DNA-PK. Analysis of these protein targets in cellular assays did not reveal any off-target activities for Torin1, WYE354, and KU63794 at concentrations below 1 μM but did show that PP242 efficiently inhibited the RET receptor (EC(50), 42 nM) and JAK1/2/3 kinases (EC(50), 780 nM). In addition, Torin1 displayed unusually slow kinetics for inhibition of the mTORC1/2 complex, a property likely to contribute to the pharmacology of this inhibitor. Our results demonstrated that, with the exception of PP242, available ATP-competitive compounds are highly selective mTOR inhibitors when applied to cells at concentrations below 1 μM and that the compounds may represent a starting point for medicinal chemistry efforts aimed at developing inhibitors of other PI3K kinase-related kinases.
Interferon-Tau Suppresses Prostaglandin F2α Secretion Independently of the Mitogen-Activated Protein Kinase and Nuclear Factor κ B Pathways1 (2001)

Pregnancy is established in ruminants through inhibitory actions of interferon (IFN)-tau on the release of prostaglandin F2alpha (PGF), which allows the corpus luteum to survive and continue to produce progesterone. Experiments were designed to 1) delineate the signal transduction pathway coordinating the synthesis of PGF, 2) determine how rapidly recombinant bovine (rb) IFN-tau attenuated phorbol ester (PDBu)-induced secretion of PGF, and 3) establish the site at which rbIFN-tau attenuates the secretion of PGF in cultured bovine endometrial (BEND) cells. BEND cells were untreated (control) or treated for 5, 10, 60, 180, or 300 min with PDBu (100 ng/ml), rbIFN-tau (50 or 500 ng/ml), PDBu + rbIFN-tau, or PDBu + PD98059 (MEK-1 inhibitor; 50 microM). Secretion of PGF was induced (P < 0.0001) by PDBu within 180 min, but induction was inhibited 74% by the addition of rbIFN-tau (P < 0.0001) and was ablated completely by PD98059. Parallel results were obtained for cyclooxygenase (COX)-2 protein expression. PDBu induced (P < 0.05) activation of the Raf-1/MEK-1/ERK-1/2 pathway, which was obligatory for the expression of COX-2 and secretion of PGF but was not altered by cotreatment with rbIFN-tau. PDBu induced (P < 0.05) transcription of c-jun and c-fos mRNAs within 30 min; induction was inhibited (P < 0.05) by cotreatment with PD98059 but not by cotreatment with rbIFN-tau. Treatment of BEND cells with rbIFN-tau also did not attenuate PDBu-induced degradation of IkappaBalpha, suggesting that the IkappaBalpha/NFkappaB pathway is not a site of IFN-tau inhibition of PGF. However, rbIFN-tau did block transcription of the COX-2 gene induced by PDBu within 30 min. In conclusion, COX-2 expression and PGF secretion induced by PDBu is mediated through the Raf-1/MEK-1/ERK-1/2 pathway, but this pathway is not disrupted by rbIFN-tau. Because rbIFN-tau inhibits COX-2 mRNA within 30 min, we hypothesized that transcription factors activated by rbIFN-tau rapidly and directly attenuate COX-2 gene expression, thereby suppressing secretion of PGF.
Specific Inhibitors of p38 Mitogen-activated Protein Kinase Block 3T3-L1 Adipogenesis (1998)

SB203580 and SB202190, pyridinyl imidazoles that selectively inhibit p38 mitogen-activated protein (MAP) kinase, are widely utilized to assess the physiological roles of p38. Here, we demonstrate that treatment of 3T3-L1 fibroblasts with these p38 MAP kinase inhibitors prevents their differentiation into adipocytes as judged by an absence of lipid accumulation, a lack of expression of adipocyte-specific genes, and a fibroblastic morphological appearance. In 3T3-L1 fibroblasts and developing adipocytes, p38 is active. p38 activity decreases dramatically during later stages of differentiation. In accordance with the time course of p38 activity, p38 inhibitor treatment during only the early stages of differentiation is sufficient to block adipogenesis. In addition, we constructed a 3T3-L1 cell line harboring an inducible dominant negative p38 mutant. The induction of this dominant negative mutant of p38 prevents adipocyte differentiation. Thus, it is likely that the antiadipogenic activity of SB203580 and SB202190 is indeed due to inhibition of p38 MAP kinase. This study points out that CCAAT/enhancer-binding protein beta (C/EBPbeta), a transcription factor critical for the initial stages of 3T3-L1 adipogenesis, bears a consensus site for p38 phosphorylation and serves as a substrate for p38 MAP kinase in vitro. Although the induction of C/EBPbeta is not significantly altered in the presence of the p38 inhibitor, the amount of in vivo phosphorylated C/EBPbeta is reduced by SB203580. The transcriptional induction of PPARgamma, a gene whose expression is induced by C/EBPbeta, and a factor critically involved in terminal differentiation of adipocytes, is impaired in the presence of p38 inhibitors. Thus, transcription factors such as C/EBPbeta that promote adipocyte differentiation may be p38 targets during adipogenesis. Collectively, the data in this study suggest that p38 MAP kinase activity is important for proper 3T3-L1 differentiation.
The Role of Neuronal Nicotinic Acetylcholine Receptors in Acute and Chronic Neurodegeneration (2002)

In the last five years there has been a rapid explosion of publications reporting that neuronal nicotinic acetylcholine receptors (nAChRs) play a role in neurodegenerative disorders. Furthermore, there is a well-established loss of nAChRs in post-mortem brains from patients with Alzheimer's disease, Parkinson's disease and a range of other disorders. In the present review we discuss the evidence that nicotine and subtype selective nAChR ligands can provide neuroprotection in in vitro cell culture systems and in in vivo studies in animal models of such disorders. Whilst in vitro data pertaining to a protective effect of nicotine against nigral neurotoxins like MPTP is less robust, most studies agree that nicotine is protective against glutamate and beta-amyloid toxicity in various culture systems. This effect appears to be mediated by alpha7 subtype nAChRs since the protection is blocked by alpha-bungarotoxin and is mimicked by alpha7 selective agonists. In vivo studies indicate that alpha7 receptors play a critical role in protection from cholinergic lesions and enhancing cognitive function. The exact subtype involved in the neuroprotectant effects seen in animal models of Parkinson's disease is not clear, but in general broad spectrum nAChR agonists appear to provide protection, while alpha4beta2 receptors appear to mediate symptomatic improvements. Evidence favouring a protectant effect of nicotine against acute degenerative conditions is less strong, though some protection has been observed with nicotine pre-treatment in global ischaemia models. A variety of cellular mechanisms ranging from the production of growth factors through to inactivation of toxins and antioxidant actions of nicotine have been proposed to underlie the nAChR-mediated neuroprotection in vitro and in vivo. In summary, although the lack of subtype selective ligands has hampered progress, it is clear that in the future neuronal nAChR agonists could provide functional improvements and slow or halt the progress of several crippling degenerative diseases.
Characterization of a co-electrospun scaffold of HLC/CS/PLA for vascular tissue engineering (2014)

Novel scaffolds for vascular tissue engineering were fabricated by co-electrospinning human-like collagen/chitosan and polylactic acid at room temperature and normal pressure. By studying the effects of composition and collecting distance on the morphology of electrospun meshes, we determined that the proper collecting distance and the concentration of the solution are the keys to the success of the co-electrospinning process. The scaffolds were characterized by scanning electron microscopy (SEM) and distribution of the fibrous diametrs was analyzed. Also, Hemocompatibility of the scaffolds were evaluated. The results indicated that scaffolds fabricated by co-electrospinning: (1) had a more biomimetic structure than polylactic acid, as the fiber diameters approached the size of the extracellular matrix; (2) showed better hemocompatibility. This study demonstrates the feasibility of using two different solutions to construct a scaffold for blood vessel tissue engineering by co-electrospinning.
Cancer in the Contralateral Breast after Radiotherapy for Breast Cancer (1992)

Radiotherapy for breast cancer contributes little to the already high risk of a second cancer in the opposite breast. Fewer than 3 percent of all second breast cancers in this study could be attributed to previous radiation treatment; the risk, however, was significantly increased among women who underwent irradiation at a relatively young age (less than 45 years). Radiation exposure after the age of 45 entails little, if any, risk of radiation-induced breast cancer.
Performance of a radio link between a base station and a medical implant utilising the MICS standard (2005)

Modern medical implants are of increasing complexity and with that, the need for fast and flexible communication with them grows. A wireless system is preferable and an inductive link is the most commonly used. But it has the drawback of a very short range, essentially limited to having the external transceiver touching the patient. The Medical Implant Communication System, MICS, is a standard aimed at improving the communication distance. It operates at a higher frequency band between 402 MHz and 405 MHz. We have by simulations and measurements investigated the channel properties of this band and calculated the link performance for a typical implant application. The result is a link speed between a base station and a bedridden patient of 600 kbit bits per second with a bit error rate of 2% in the downlink to the implant and 1 % in the uplink to the base station. Conclusions on the necessary complexity of the base station are also given.
Novel application of vacuum assisted closure technique to the treatment of sternotomy wound infection (2000)

Infection of the sternotomy wound is a potentially devastating and sometimes lethal complication following cardiac surgery. Established treatment may involve a combination of debridement, packing, delayed closure, plastic reconstruction, re-wiring and irrigation dependent on the severity of infection. Vacuum assisted closure, originally adopted for the treatment of non-healing wounds, has recently gained popularity among various surgical specialities in managing complex wound infection. Here we describe this novel technique of managing postoperative sternal wound infection.