gebhart/patrepeval huggingface dataset:
Development and evaluation of 5FUCore, OxaliCore, and IrinoCore transcriptomic signatures for predicting response to individual drugs in the FOLFIRINOX regimen: Towards toxicity reduction and personalized chemotherapy in PDAC. (2023)

4141 Background: Recently, we have successfully developed a transcriptomic signature that predicts the response to gemcitabine treatment in patients with localized pancreatic ductal adenocarcinoma (PDAC) (PMID: 36178036) and also in those with metastatic PDAC (PMID: 36496056). This was achieved by using an approach that combined several preclinical PDAC models. The FOLFIRINOX regimen (FFX) consisting of 5-Fluorouracil (5FU), Oxaliplatin, and Irinotecan is the more effective treatment option, but the high toxicity limits its use. In this study, we developed and analyzed three different transcriptomic signatures for the drugs composing FFX separately and evaluated their clinical utility. Methods: We combined the transcriptomic profile of 14 patients derived xenograft (PDX) and 31 patients derived cell cultures (PDC) with their corresponding chemotherapy response profiles. We developed predictive signatures for 5FU ( 5FUCore), Oxaliplatin ( OxaliCore), and Irinotecan ( IrinoCore), as previously reported for the GemCore signature (PMID: 36178036). They were then validated in three independent cohorts of patients: COMPASS (n = 94), Linehan (n = 28), and a new cohort of 87 advanced PDAC patients. Results: Three ICA components that reflect the chemotherapy response profiles for 5FU, oxaliplatin, and irinotecan were evaluated in the COMPASS cohort to determine their ability to identify sensitive patients in the FFX arm. Patients predicted as sensitive to each drug separately had a median overall survival (OS) of 77.6 (95% CI, 67.9-NR, P =0.02), 78.7 (95% CI, 57.6-NR, P= 0.002), and 70.4 (95% CI, 57.6-NR, P= 0.02) months for 5FU, oxaliplatin, and irinotecan, respectively. Notably, the model that integrated the group of sensitive patients to two or three drugs had the highest median OS in the COMPASS and Linehan cohorts with a HR of 0.25 (95% CI, 0.11-0.57; P &lt; 0.001) and 0.11 (95% CI, 0.02-0.70; P= 0.019), respectively. Importantly, they also show a better objective response than the other groups ( P= 0.009). In the advanced PDAC group, the signatures showed a strong ability to discriminate sensitive patients in the FFX arm with a median OS of 20.1 (95% CI, 2.3-NR, P= 0.006), 13.64 (95% CI, 9.57-NR, P= 0.003), and 15.87 (95% CI, 2.9-NR, P= 0.002) months for 5FU, oxaliplatin, and irinotecan, respectively. Finally, we evaluated the best combination of two drugs in the pooled group. Patients sensitive to both 5FU and oxaliplatin showed the best response with 60% of patients achieving partial response. Conclusions: The signatures developed provide a tool for predicting responsiveness to the individual therapeutic drugs of the FFX regimen. They may ultimately lead to the development of a personalized strategy for combined chemotherapy regimens, increasing efficacy and reducing toxicity in PDAC.
ChemInform Abstract: Stereochemistry of Nucleophilic Epoxidation of (S)‐2‐p‐Tolylsulfonyl‐2‐ cyclohexenol and O‐Derivatives. (1993)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
JigDFS: A secure distributed file system (2009)

Ubiquitous connectivity and availability of P2P resources creates opportunities for building new services. This paper describes Jigsaw Distributed File System (JigDFS) which can be used to securely store and retrieve files on a P2P network anonymously. JigDFS is designed to provide strong encryption and a certain level of plausible deniability. Files in JigDFS are sliced into small segments using an information dispersal algorithm (IDA) and distributed onto different nodes recursively to increase fault tolerance against node failures. Moreover, layered encryption is applied to each file with keys produced by a hashed-key chain algorithm, so that data (file segments) and keys reside on different hosts. In such a scheme, if an attacker compromises a host and retrieves the data, the attacker will still need the correct key to decipher the data. Furthermore, recursive IDA and layered encryption ensure users' anonymity. It is difficult for an adversary to identify who owns a file, even who has retrieved a file in JigDFS. Often, a strong adversary may have the power to monitor the network or even force a user to give up the password. Design of JigDFS provides users with plausible deniability which enhances privacy. When being questioned, a JigDFS user can simply argue that he/she is merely a relaying node, rather than the file owner. Moreover, a user, when forced, can give up a valid, however, incorrect encryption key. There is no way for an adversary to verify either correctness of a key or the identity of file owner. JigDFS is developed using platform independent Java technologies and is envisioned to utilize mobile computing elements such as PDAs and smart phones.
Fiber nonlinearity compensation for OFDM super-channels using optical phase conjugation (2012)

We experimentally demonstrate that mid-link optical phase conjugation (OPC) effectively compensates fiber nonlinearity in coherent optical OFDM super-channels. The OPC was produced by pump × subcarrier degenerate four-wave-mixing in a 1-km highly nonlinear fiber. The nonlinear threshold for the 10 × 80-km 604.7-Gb/s 16-QAM test system was increased by 4.8 dB. The performance at the optimum power was only improved by 0.2 dB because the OPC module produces a 1.6 dB penalty for the back-to-back system. FWM theory shows that the 'noise' processes of OPC modules utilizing χ3 nonlinearities could be reduced by increasing the pump power, which will improve back-to-back performance with the OPC module.
Frequency Shift Chirp Modulation with Additional Differential Phase Shift Keying (2019)

The article discusses a method for increasing the spectral efficiency and noise immunity of Multiple Frequency Shift Chirp Modulation by combining with Differential Phase Shift Keying for the initial phase of the chirp symbol. An optimal non-coherent demodulation method based on the Fourier transform is presented.
Polycarbonate and polystyrene nanoplastic particles act as stressors to the innate immune system of fathead minnow (Pimephales promelas) (2016)

Water pollution with large-scale and small-scale plastic litter is an area of growing concern. Macro-plastic litter is a well-known threat to aquatic wildlife; however, the effects of micro-sized and nano-sized plastic particles on the health of organisms are not well understood. Small-scale plastic particles can easily be ingested by various aquatic organisms and potentially interfere with their immune system; therefore, the authors used a freshwater fish species as a model organism for nanoplastic exposure. Characterization of polystyrene (41.0 nm) and polycarbonate (158.7 nm) nanoplastic particles (PSNPs and PCNPs, respectively) in plasma was performed, and the effects of PSNPs and PCNPs on the innate immune system of fathead minnow were investigated. In vitro effects of PSNPs and PCNPs on neutrophil function were determined using a battery of neutrophil function assays. Exposure of neutrophils to PSNPs or PCNPs caused significant increases in degranulation of primary granules and neutrophil extracellular trap release compared to a nontreated control, whereas oxidative burst was less affected. The present study outlines the stress response of the cellular component of fish innate immune system to polystyrene and polycarbonate nanoparticles/aggregates and indicates their potential to interfere with disease resistance in fish populations. Environ Toxicol Chem 2016;35:3093-3100. © 2016 SETAC.
Urea Fluctuations in Stream Baseflow across Land Cover Gradients and Seasons in a Coastal Plain River System (2018)

Abstract Urea‐N is a component of bioavailable dissolved organic nitrogen (DON) that contributes to coastal eutrophication. In this study, we assessed urea‐N in baseflow across land cover gradients and seasons in the Manokin River Basin on the Delmarva Peninsula. From March 2010 to June 2011, we conducted monthly sampling of 11 streams (4 tidal and 7 nontidal), 2 wastewater treatment plants, an agricultural drainage ditch, and groundwater underlying a cropped field. At each site, we measured urea‐N, DON, dissolved organic carbon (DOC), total dissolved nitrogen (TDN), NO 3 − ‐N, and NH 4 + ‐N. In general, urea‐N comprised between 1% and 6% of TDN, with the highest urea‐N levels in drainage ditches (0.054 mg N/L) and wetland‐dominated streams (0.035–0.045 mg N/L). While urea‐N did not vary seasonally in tidal rivers, nontidal streams saw distinct urea‐N peaks in summer (0.038 mg N/L) that occurred several months after cropland fertilization in spring. Notably, the proportion of wetlands explained 78% of the variance in baseflow urea‐N levels across the Manokin watershed. In wetland‐dominated basins, we found urea‐N was positively related to water temperature and negatively related to DOC:DON ratios, indicating short‐term urea‐N dynamics at baseflow were more likely influenced by instream and wetland‐driven processes than by recent agricultural urea‐N inputs. Findings demonstrate important controls of wetlands on baseflow urea‐N concentrations in mixed land‐use basins.
Design of μ selective opioid dipeptide antagonists (1997)

We have recently designed potent delta selective opioid antagonist dipeptides on the basis of a simple conformational analysis. Following a similar procedure we found a mu selective dipeptide antagonist, 2,6-dimethyl-Tyr-D-Phe-NH2. Although its selectivity is not as high as those of the quoted delta selective dipeptides it has good in vitro activity and looks very promising for further development since the 2,6-dimethyl-Tyr-D-Phe message, like the delta selective 2,6-dimethyl-Tyr-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid counterpart, seems able to impart antagonism to longer peptides.
Advancing tissue-engineered vascular grafts via their endothelialization and mechanical conditioning (2020)

Tissue engineering has garnered significant attention for its potential to address the predominant modes of failure of small diameter vascular prostheses, namely mid-graft thrombosis and anastomotic intimal hyperplasia. In this review, we described two main features underpinning the promise of tissue-engineered vascular grafts: the incorporation of an antithrombogenic endothelium, and the generation of a structurally and biomechanically mimetic extracellular matrix. From the early attempts at the in-vitro endothelialization of vascular prostheses in the 1970s through to the ongoing clinical trials of fully tissue-engineered vascular grafts, the historical advancements and unresolved challenges that characterize the current state-of-the-art are summarized in a manner that establishes a guide for the development of an effective vascular prosthesis for small diameter arterial reconstruction. The importance of endothelial cell purity and their arterial specification for the prevention of both diffuse neointimal hyperplasia and the accelerated development of atherosclerotic lesions is delineated. Additionally, the need for an extracellular matrix that recapitulates both the composition and structure of native elastic arteries to facilitate the protracted stability and patency of an engineered vasoactive conduit is described. Finally, the capacity of alternative sources of cells and mechanical conditioning to overcome these technical barriers to the clinical translation of an effective small diameter vascular prosthesis is discussed. In conclusion, this review provides an overview of the historical development of tissue-engineered vascular grafts, highlighting specific areas warranting further research, and commentating on the outlook of a clinically feasible and therapeutically efficacious vascular prosthesis for small diameter arterial reconstruction.
A hydrogen peroxide-generating agent, 6-formylpterin, enhances heat-induced apoptosis (2005)

The enhancement of heat-induced apoptosis by 6-formylpterin, an intra-cellular generator of hydrogen peroxide (H2O2), was examined in human myelomonocytic lymphoma U937 cells. The cells were treated with either 6-formylpterin alone at a nontoxic concentration of 300 microM (37 degrees C), heat shock (44 degrees C per 20 min) alone or a combination of the two, then incubated at 37 degrees C for 6 h. Assessments of apoptosis, mitochondrial membrane potential and caspase-3 activation were performed by flow cytometry. Moreover, caspase-8 activation and changes in the intra-cellular Ca2+ concentration ([Ca2+]i) were examined. Bax, Bcl-2, Bcl-XL, Bid, cytochrome c and PKCd were detected by Western blotting. The induction of heat-induced apoptosis evaluated by morphological observation and DNA fragmentation were promoted by the addition of 6-formylpterin. Mitochondrial membrane potential was decreased and the activation of caspase-3 and -8 was enhanced in the cells treated with the combination. A decreased-expression of Bid was noted, although no significant changes in Bax, Bcl-2 and Bcl-XL expression were observed after the combined treatment. Furthermore, both the release of cytochrome c from mitochondria to cytosol and the translocation of PKCd from cytosol to mitochondria, which were induced by heat shock, were enhanced by the addition of 6-formylpterin. The number of cells with a higher [Ca2+]i was also increased by the addition of 6-formylpterin. These findings suggest that the increase in [Ca2+]i, the activation of the mitochondria-caspase dependent pathway and the translocation of PKCd to mitochondria play principal roles in the enhancement of heat-induced apoptosis by 6-FP.
The Role of AGEs and AGE Inhibitors in Diabetic Cardiovascular Disease (2005)

Prolonged hyperglycemia, dyslipidemia and oxidative stress in diabetes result in the production and accumulation of AGEs. It is now clear that AGEs contribute to the development and progression of cardiovascular disease in diabetes, as well as other complications. AGEs are thought to act through receptor-independent and dependent mechanisms to promote vascular damage, fibrosis and inflammation associated with accelerated atherogenesis. As a result, novel therapeutic agents to reduce the accumulation of AGEs in diabetes have gained interest as potential cardioprotective approaches. A variety of agents have been developed which are examined in detail in this review. These include aminoguanidine, ALT-946, pyridoxamine, benfotiamine, OPB-9195, alagebrium chloride, N-phenacylthiazolium bromide and LR-90. In addition, it has been demonstrated that a number of established therapies have the ability to reduce the accumulation of AGEs in diabetes including ACE inhibitors, angiotensin receptor antagonists, metformin, peroxisome proliferators receptor agonists, metal chelators and some antioxidants. The fact that many of these inhibitors of AGEs are effective in experimental models, despite their disparate mechanisms of action, supports the keystone role of AGEs in diabetic vascular damage. Nonetheless, the clinical utility of AGE inhibition remains to be firmly established. Optimal metabolic and blood pressure control, that is achieved early and sustained indefinitely, remains the best recourse for inhibition of AGEs until more specific interventions become a clinical reality.
Selective Hydrocarbon Oxidation in Zeolites (2007)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
On the automated multiple liquid bottle filling system (2016)

This paper presents automated Multiple Liquid Bottle Filling (MLBF) system in which liquid is filled depending upon the color of bottle. The manual system of bottle filling cannot be applied in modern industries with bulk filling requirements as the process can consume considerable time and may causing spilling or wastage of the products. Consistency in filling of the bottles can also be yet another issue rising out of the manual bottle filling processes. The Automatic systems provide a viable solution to overcome the drawback of manual Systems. But, the existing Automatic Liquid Bottle Filling (LBF) systems are unable to fill multiple liquids using single system. The peculiar feature of proposed automatic system is that, multiple liquids can be filled using single system. The experimental set up is designed for filling two liquids, depending upon the color of bottles, using Siemens S7-1200 Programmable logic controller (PLC).
The Effects of Plyometric vs. Dynamic Stabilization and Balance Training on Power, Balance, and Landing Force in Female Athletes (2006)

Neuromuscular training protocols that include both plyometrics and dynamic balance exercises can significantly improve biomechanics and neuromuscular performance and reduce anterior cruciate ligament injury risk in female athletes. The purpose of this study was to compare the effects of plyometrics (PLYO) versus dynamic stabilization and balance training (BAL) on power, balance, strength, and landing force in female athletes. Either PLYO or BAL were included as a component of a dynamic neuromuscular training regimen that reduced measures related to ACL injury and increased measures of performance. Nineteen high school female athletes participated in training 3 times a week for 7 weeks. The PLYO (n = 8) group did not receive any dynamic balance exercises and the BAL (n = 11) group did not receive any maximum effort jumps during training. Pretraining vs. posttraining measures of impact force and standard deviation of center of pressure (COP) were recorded during a single leg hop and hold. Subjects were also tested for training effects in strength (isokinetic and isoinertial) and power (vertical jump). The percent change from pretest to posttest in vertical ground reaction force was significantly different between the BAL and PLYO groups on the dominant side (p < 0.05). Both groups decreased their standard deviation of center of pressure (COP) during hop landings in the medial/lateral direction on their dominant side, which equalized pretested side to side differences. Both groups increased hamstrings strength and vertical jump. The results of this study suggest that both PLYO and BAL training are effective at increasing measures of neuromuscular power and control. A combination of PLYO and BAL training may further maximize the effectiveness of preseason training for female athletes.
Neutrophil activation is confined to the maternal circulation in pregnancy‐induced hypertension (1992)

The aim of this study was to determine whether neutrophil activation occurs in the fetal circulation in pregnancy-induced hypertension and to correlate this with evidence of neutrophil activation in the maternal circulation. Twenty-one normal pregnancies and 23 complicated by pregnancy-induced hypertension were studied in the third trimester. The mean length of gestation at delivery was significantly shorter (P less than .01) and the mean birth weight percentile was significantly lower (P less than .05) in the hypertensive group; otherwise the groups were comparable. Blood was obtained before cesarean delivery or established labor in the mothers and immediately after delivery from the umbilical vein. Plasma neutrophil elastase, which is released after neutrophil activation, was measured by radioimmunoassay as a marker for neutrophil activation. The mean (+/- standard error) concentration of neutrophil elastase in maternal plasma in the hypertensive group (35.9 +/- 4.7 ng/mL) was significantly higher than in the normal group (20.8 +/- 0.87 ng/mL) (P less than .005). The concentration of neutrophil elastase in umbilical venous plasma was not significantly different between the normal and hypertensive groups. However, significantly higher concentrations of neutrophil elastase were found in the umbilical venous plasma of pregnancies delivered vaginally compared with those delivered by cesarean (P less than .05) regardless of diagnosis. There was no correlation between maternal venous and umbilical venous plasma neutrophil elastase concentrations, birth weight percentile, plasma urate, or platelet count. These data suggest that neutrophil activation is confined to the maternal circulation in pregnancy-induced hypertension where it may contribute to vascular damage and dysfunction in areas such as the placental bed.(ABSTRACT TRUNCATED AT 250 WORDS)
Time-of-Flight Experiments in Molecular Motion and Electron-Atom Collision Kinematics (1971)

A set of experiments for an undergraduate laboratory which demonstrate the relationship between velocity, mass, and temperature in a gas is described. The experimental method involves time-of-flight measurements on atoms excited to metastable states by electron impact. Effects resulting from recoil in the electron-atom collision can also be observed. A suitable apparatus for conducting the experiments is described.
Estimating customer impatience in a service system with balking (2020)

This paper studies a service system in which arriving customers are provided with information about the delay they will experience. Based on this information they decide to wait for service or to leave the system. The main objective is to estimate the customers' patience-level distribution and the corresponding potential arrival rate, using knowledge of the actual workload process only. We cast the system as a queueing model, so as to evaluate the corresponding likelihood function. Estimating the unknown parameters relying on a maximum likelihood procedure, we prove strong consistency and derive the asymptotic distribution of the estimation error. Several applications and extensions of the method are discussed. In particular, we indicate how our method generalizes to a multi-server setting. The performance of our approach is assessed through a series of numerical experiments. By fitting parameters of hyperexponential and generalized-hyperexponential distributions our method provides a robust estimation framework for any continuous patience-level distribution.
A k-generation approach to wireless fingerprinting for position estimation (2014)

Traditional approaches to pattern based positioning have proposed schemes specifically tailored for the area of interest in which they are employed. Many, when applied to a generic search environment, may not scale computationally due to either a very large tracking area, very fine granularity in the database, or both. Here, a novel framework for fingerprinting that utilizes a k-generation structure is proposed. This significantly reduces the required number of computations while maintaining comparable accuracy to the traditionally used single-generation approach. This is the key enabler that allows generalization of our framework to any search space. We validate this approach through simulation and show that the a multigeneration approach indeed provides computational gains while simultaneously maintaining accuracy. Second, we show how a natural grouping of constituent members can improve accuracy. We use graph spectral partitioning to demonstrate this effect. The end result is a framework that can be generalized to any size search space with an arbitrary level of granularity.
Economic burden of cardiovascular diseases in the enlarged European Union (2006)

CVD is a leading public health problem. Our study is the first to assess the economic burden of CVD across the EU, and our results should help policy makers evaluate policy impact and prioritize research expenditures. However, because of data unavailability, our study has important limitations, which highlight the need for more accurate and comparable CVD-specific information.