gebhart/patrepeval huggingface dataset:
SELECT: A multicenter phase II trial of adjuvant erlotinib in resected early-stage EGFR mutation-positive NSCLC. (2014)

7514 Background: EGFR mutant NSCLC is exquisitely sensitive to EGFR tyrosine kinase inhibitors (TKIs). Retrospective data suggests adjuvant TKIs may improve outcomes. This trial is the first to prospectively test the efficacy of adjuvant erlotinib in EGFR-mutant NSCLC. Methods: Eligible pts had resected stage IA-IIIA NSCLC harboring a TKI-sensitizing EGFR mutation. Pts were treated with erlotinib 150 mg/day for 2 years after completion of standard adjuvant chemotherapy and/or radiotherapy. With a sample size of 100 pts the study was powered to demonstrate a primary endpoint of 2-year disease free survival (DFS) >85%, compared to a historical control of 76% in resected early-stage EGFR-mutant NSCLC. Results: 100 pts were enrolled at 7 sites between 1/08 and 5/12; 45% stage I; 27% stage II; 28% stage IIIA. 89 pts have reached 2 year follow-up (2 year follow-up on the entire cohort will be presented at the annual meeting). Toxicities were typical of erlotinib with no G4/5 events and 1 G2 pulmonary fibrosis. 40% of pts required dose reduction to 100 mg/day and 16% two dose reductions to 50 mg/day. 69% of pts completed at least 22 months of erlotinib. With median follow-up of 3 years, the 2-year DFS is 90% (97% stage 1, 73% stage 2, 92% stage 3). Median DFS and OS have not been reached. 24 pts have recurred, only 2 during erlotinib treatment and 22 after stopping erlotinib with a median time to recurrence of 12 months after stopping erlotinib. 63% (n=15) of pts with recurrence underwent repeat biopsy, and only 1 T790M was detected. 71% (n=17) of recurrent pts were re-treated with erlotinib with 10 pts remaining on erlotinib, treatment range 2-42 months. 8 pts have died. Conclusions: Pts with EGFR mutation-positive NSCLC treated with adjuvant erlotinib have an improved 2-year DFS compared to historical genotype-matched controls. Recurrences are rare on erlotinib and most occur in the 12m after discontinuation, suggesting longer duration of adjuvant treatment may be beneficial. Recurrent cases after adjuvant erlotinib remain generally sensitive to EGFR TKIs. Clinical trial information: NCT00567359.
A simplified multi-wavelength ESPI contouring technique based on a diode laser system (1992)

A simplified multi-wavelength ESPI contouring technique using a diode laser source has been demonstrated to be a useful tool in the shape measurement of an object. Unlike other type of two-wavelength ESPI contouring systems, the technique described in this paper does not required a master-wavefront illumination and the conjugate condition imposed on the reference beam, the experiment procedure is, therefore, considerably simplified. Instead of modulating the injection current of the diode laser, the alternation of wavelength is achieved by adjusting the temperatures applied to the laser diode so that the problem of visibility reduction due to intensity variations of speckle pattern can be overcome. In addition, the decorrelation effect due to the wavelength change in this specific ESPI contouring system is also analyzed quantitatively in order to show the limitations of this technique on practical applications. Contour fringes of a pyramid, as an example, are obtained from experiments, which are in agreement with theoretical analysis.
Membrane Recycling by Coated Vesicles (1981)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Erasure coding for real-time streaming (2012)

We consider a real-time streaming system where messages are created sequentially at the source, and are encoded for transmission over a packet erasure channel. Each message must subsequently be decoded at the receiver within a given delay from its creation time. We consider code design and maximum message rates when all messages must be decodable by their respective deadlines under a specified set of erasure patterns (erasure model). Specifically, we provide a code construction that achieves the optimal rate for an asymptotic number of messages, under erasure models containing a limited number of erasures per coding window, per sliding window, and containing erasure bursts of a limited length.
Infusion of freshly isolated autologous bone marrow derived mononuclear cells prevents endotoxin-induced lung injury in an ex-vivo perfused swine model (2013)

We conclude that infusion of freshly isolated autologous whole bone marrow cells and the subset of non-hematopoietic cells can suppress the acute humoral and physiologic responses induced by endotoxemia by modulating the inflammatory response, mechanisms that do not involve engraftment or trans-differentiation of the cells. These observations may have important implications for the design of future cell therapies for ARDS.
An EP2 receptor-selective prostaglandin E2agonist induces bone healing (2003)

The morbidity and mortality associated with impaired/delayed fracture healing remain high. Our objective was to identify a small nonpeptidyl molecule with the ability to promote fracture healing and prevent malunions. Prostaglandin E2 (PGE2) causes significant increases in bone mass and bone strength when administered systemically or locally to the skeleton. However, due to side effects, PGE2 is an unacceptable therapeutic option for fracture healing. PGE2 mediates its tissue-specific pharmacological activity via four different G protein-coupled receptor subtypes, EP1, -2, -3, and -4. The anabolic action of PGE2 in bone has been linked to an elevated level of cAMP, thereby implicating the EP2 and/or EP4 receptor subtypes in bone formation. We identified an EP2 selective agonist, CP-533,536, which has the ability to heal canine long bone segmental and fracture model defects without the objectionable side effects of PGE2, suggesting that the EP2 receptor subtype is a major contributor to PGE2's local bone anabolic activity. The potent bone anabolic activity of CP-533,536 offers a therapeutic alternative for the treatment of fractures and bone defects in patients.
Adaptive Provisioning of Stream Processing Systems in the Cloud (2012)

With the advent of data-intensive applications that generate large volumes of real-time data, distributed stream processing systems (DSPS) become increasingly important in domains such as social networking and web analytics. In practice, DSPSs must handle highly variable workloads caused by unpredictable changes in stream rates. Cloud computing offers an elastic infrastructure that DSPSs can use to obtain resources on-demand, but an open problem is to decide on the correct resource allocation when deploying DSPSs in the cloud. This paper proposes an adaptive approach for provisioning virtual machines (VMs) for the use of a DSPS in the cloud. We initially perform a set of benchmarks across performance metrics such as network latency and jitter to explore the feasibility of cloud-based DSPS deployments. Based on these results, we propose an algorithm for VM provisioning for DSPSs that reacts to changes in the stream workload. Through a prototype implementation on Amazon EC2, we show that our approach can achieve low-latency stream processing when VMs are not overloaded, while adjusting resources dynamically with workload changes.
The shade avoidance syndrome: multiple responses mediated by multiple phytochromes (1997)

ABSTRACT In recent years, the concept of shade avoidance has provided a functional meaning to the role of the phytochrome photoreceptor family in mature plants in their natural environment, and the question of which of these phytochromes is responsible for shade avoidance reactions has inevitably been raised. Unfortunately, a misconception has arisen that phytochrome B is solely responsible for detecting the environmental signal that initiates the shade avoidance syndrome. This view is too simplistic, and is based upon a selective interpretation of the available evidence. In this short Commentary, we review the concept of the shade avoidance syndrome, show how the misconception arose, and emphasize the plurality of perception and response that is crucial to successful competition for light.
CONNEXIN43 GAP JUNCTION LEVELS DURING DEVELOPMENT OF THE THORACIC AORTA ARE TEMPORALLY CORRELATED WITH ELASTIC LAMINAE DEPOSITION AND INCREASED BLOOD PRESSURE (1997)

A characteristic property of the vascular smooth muscle cell is its ability to modulate between a contractile phenotype, responsible for control of vascular tone, through to a synthetic phenotype, capable of migration and synthesis of extracellular matrix molecules. Smooth muscle cells are coupled by gap junctions, the membrane structures which permit direct intercelluar passage of ions and small molecules, and which play a role both in electrical coupling and intercellular communication during patterning and development. We have previously found that connexin43 type gap junction expression is upregulated in the synthetic phenotype smooth muscle cell in vitro and during atherosclerotic plaque formation in human coronary arteries. On the basis of immunohistochemical labelling, confocal laser scanning microscopy and digital image analysis, we now report that relatively high levels of connexin43 are expressed during development of the rat thoracic aorta, temporally correlating with reported periods of smooth muscle cell proliferation and secretion of elastic laminae. A major peak in expression occurs at seven days post-natal, with a second less pronounced peak at 72 days post-natal. The principal peak in gap junction levels appears to coincide with increased post-natal blood pressure and aorta media thickening. The amount of gap junction labelling falls off to normal adult levels as the smooth muscle cells modulate towards the contractile phenotype and growth is completed. The results indicate an association between direct cell-to-cell communication and synthetic phenotype smooth muscle cell activity during aortic growth and patterning.
New treatments for inflammatory bowel disease (1998)

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The use of near-infrared light for safe and effective visualization of subsurface blood vessels to facilitate blood withdrawal in children (2012)

Obtaining access to blood vessels can be difficult, especially in children. Visualization of subsurface blood vessels might be a solution. Ultrasound and visible light have been used to this purpose, but have some drawbacks. Near-infrared light might be a better option since subsurface blood vessels can be visualized in high contrast due to less absorption and scattering in tissue as compared to visible light. Our findings with a multispectral imaging system support this theory. A device, the VascuLuminator, was developed, based on transillumination of the puncture site with near-infrared light. The VascuLuminator was designed to meet the requirements of compact and safe use. A phantom study showed that the maximum depth of visibility (5.5mm for a 3.6mm blood vessel) is sufficient to visualize blood vessels in typical locations for peripheral venous and arterial access. A quantitative comparison of the VascuLuminator and to two other vessel imaging devices, using reflection of near-infrared light instead of transillumination, was conducted. The VascuLuminator is able to decrease failure at first attempt in blood withdrawal in pediatric patients from 10/80 (13%) to 1/45 (2%; P=.05).
Role of RLIP76 in lung cancer doxorubicin resistance: III. Anti-RLIP76 antibodies trigger apoptosis in lung cancer cells and synergistically increase doxorubicin cytotoxicity (2003)

RLIP76 (ral-binding protein, RalBP1) is a non-ABC multi-specific transporter of amphiphilic chemotherapeutic drugs such as doxorubicin (DOX) and glutathione-electrophile conjugates. In the present studies, we used polyclonal rabbit anti-human RLIP76 IgG to inhibit RLIP76 function for determining the role of RLIP76 in DOX resistance of NSCLC cells. Western blot analyses and immunohistochemistry studies showed no recognition of other protein in crude NSCLC cell homogenates by anti-RLIP76, confirming the specificity of anti-RLIP76 IgG. In immunohistochemistry and flow cytometry studies, these antibodies recognized RLIP76 domain(s) on the cell surface. Cells coated with anti-RLIP76 IgG accumulated significantly greater DOX than cells coated with pre-immune IgG. Synergy was calculated using the Chou-Talalay median effect analysis. Herceptin was the positive control, and pre-immune IgG and Rituxan (anti-CD20) were negative controls. The interaction of anti-RLIP76 IgG and DOX were markedly synergistic (CI 0.36+/-0.27). Lesser synergy was observed between Herceptin and DOX (CI 0.75+/-0.49). Interaction between Herceptin and anti-RLIP76 was only additive (CI 1.12+/-0.5). Human IgG, Rituxan, and rabbit pre-immune IgG controls had no effect on DOX toxicity. DNA-laddering confirmed that DOX triggered apoptosis. Anti-RLIP76 IgG alone as well as Herceptin alone also triggered apoptosis in all 6 NSCLC cell lines. Anti-RLIP76 IgG and Herceptin were shown to increase DOX accumulation in NSCLC. These results demonstrated that specific inhibition of the transport function of RLIP by anti-RLIP76 IgG can trigger apoptosis and synergistically increase DOX cytotoxicity in NSCLC.
Association of an Extracellular Matrix Gene Cluster with Breast Cancer Prognosis and Endocrine Therapy Response (2008)

FN1, LOX, SPARC, and TIMP3 expression levels are associated with the prognosis of patients with breast cancers, whereas TNC is associated with resistance to tamoxifen therapy. Further validation and functional studies are necessary to determine the use of these ECM genes in decisions regarding treatment and whether they can serve as targets for therapy.
Proton radiotherapy with the Uppsala cyclotron. Experience and plans. (1985)

From 1957 to 1968, the 230-cm synchrocyclotron at the Gustaf Werner Institute was used for clinical tests with a 185 MeV proton beam. The radiotherapeutic research was part of an extensive research programme in physics, chemistry, biology and medicine. Only a small series of patients were treated. A brief review of the early development and clinical experience of the cyclotron activities at Uppsala from 1957 to 1968 is given. The former accelerator is now being converted. Beams are expected to be available in the new radiotherapy treatment rooms in 1986. Plans for the new facilities with special reference to alternative methods of proton acceleration and beam transport, i.e. fixed beams or an gantry system are presented. The corresponding activities at the Institute of Theoretical and Experimental Physics (ITEP) in Moscow are also referred to thanks to a bilateral research programme which has existed in the past and from which the Uppsala group has benefited greatly.
A Neural-Network-Based Model for the Dynamic Simulation of the Tire/Suspension System While Traversing Road Irregularities (2008)

This paper deals with the simulation of the tire/suspension dynamics by using recurrent neural networks (RNNs). RNNs are derived from the multilayer feedforward neural networks, by adding feedback connections between output and input layers. The optimal network architecture derives from a parametric analysis based on the optimal tradeoff between network accuracy and size. The neural network can be trained with experimental data obtained in the laboratory from simulated road profiles (cleats). The results obtained from the neural network demonstrate good agreement with the experimental results over a wide range of operation conditions. The NN model can be effectively applied as a part of vehicle system model to accurately predict elastic bushings and tire dynamics behavior. Although the neural network model, as a black-box model, does not provide a good insight of the physical behavior of the tire/suspension system, it is a useful tool for assessing vehicle ride and noise, vibration, harshness (NVH) performance due to its good computational efficiency and accuracy.
Dynamic Kinetic Resolution of α-Hydroxy Acid Esters (2000)

[formula: see text] Enzymatic resolution in combination with ruthenium-catalyzed racemization of the substrate led to dynamic kinetic resolution of alpha-hydroxy esters in good yields and excellent ee's. Studies of different parameters showed that the best results were obtained using Pseudomonas cepacia lipase, ruthenium catalyst 3, and 4-chlorophenyl acetate as acyl donor in cyclohexane.
Neurodegeneration and Inflammation (2008)

Recent studies have demonstrated a strong link between neurodegeneration and chronic inflammation. The central nervous system (CNS) has very limited regenerative capacity. Neural cell death occurs by apoptosis and necrosis. Necrosis in the CNS usually follows ischemic or traumatic brain injury. Apoptosis is known as programmed cell death and often demonstrates histologic features of acute and chronic neurologic diseases. The innate immune response is protective to the CNS to defend against pathogens. Temporary up-regulation of inflammatory events is natural and does not lead to cell death. If this inflammatory process is up-regulated, neurodegenerative changes may occur. There has been a proven link between the inflammatory response, increased cytokine formation, and neurodegeneration. Both pharmaceutic and nutrition interventions for treating chronic neurodegenerative diseases, such as Alzheimer's disease or multiple sclerosis, will be focused on reducing or terminating the chronic inflammatory response.
Riboflavin Enhances Photo‐oxidation of Amino Acids under Simulated Clinical Conditions (1983)

In neonatal nurseries, solutions of amino acids with added vitamins may be exposed to relatively intense light from phototherapy units. Light, especially in the presence of photosensitizers such as certain vitamins, is capable of destroying amino acids. In the present study, the effect of riboflavin on amino acid concentrations in solutions exposed to light was studied. Solutions of crystalline amino acids with and without added riboflavin were infused into shielded collecting vessels for 24 hr under conditions simulating those occurring during phototherapy. Decreases in concentrations of some amino acids were observed with light exposure alone. Decreases in concentrations of methionine, proline, tryptophan, and tyrosine were significantly greater in the presence of riboflavin that in its absence. Riboflavin concentrations were also significantly reduced after light exposure. Although the losses of amino acids are probably not nutritionally significant, the photo-oxidation products are largely unknown and may be toxic.
Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats (2005)

Increased intestinal permeability has been observed in numerous human autoimmune diseases, including type-1 diabetes (T1D) and its' animal model, the BB-wor diabetic prone rat. We have recently described zonulin, a protein that regulates intercellular tight junctions. The objective of this study was to establish whether zonulin-dependent increased intestinal permeability plays a role in the pathogenesis of T1D. In the BB diabetic-prone rat model of T1D, intestinal intraluminal zonulin levels were elevated 35-fold compared to control BB diabetic-resistant rats. Zonulin up-regulation was coincident with decreased small intestinal transepithelial electrical resistance, and was followed by the production of autoantibodies against pancreatic beta cells, which preceded the onset of clinically evident T1D by approximately 25 days. In those diabetic prone rats that did not progress to diabetes, both intraluminal zonulin and transepithelial electrical resistance were similar to those detected in diabetic-resistant animal controls. Blockade of the zonulin receptor reduced the cumulative incidence of T1D by 70%, despite the persistence of intraluminal zonulin up-regulation. Moreover, treatment responders did not seroconvert to islet cell antibodies. Combined together, these findings suggest that the zonulin-induced loss in small intestinal barrier function is involved in the pathogenesis of T1D in the BB diabetic-prone animal model.
In Vitro Activity of the Histatin Derivative P-113 against Multidrug-Resistant Pathogens Responsible for Pneumonia in Immunocompromised Patients (2005)

The in vitro activity of the histatin derivative P-113, alone or combined with eight antibiotics, was investigated against multidrug-resistant strains isolated from clinical specimens of immunocompromised patients with pneumonia. The gram-negative isolates were susceptible to P-113. S. aureus showed less susceptibility. Synergy was demonstrated when P-113 was combined with beta-lactams against gram-negative organisms.
Behavioral recovery from spinal cord injury following delayed application of polyethylene glycol (2002)

Topical application of the hydrophilic polymer polyethylene glycol (PEG) to isolated adult guinea pig spinal cord injuries has been shown to lead to the recovery of both the anatomical integrity of the tissue and the conduction of nerve impulses through the lesion. Furthermore, a brief (2 min) application of the fusogen (M(r) 1800, 50 % w/v aqueous solution) to the exposed spinal cord injury in vivo can also cause rapid recovery of nerve impulse conduction through the lesion in association with functional recovery. Behavioral recovery was demonstrated using a long-tract, spinal-cord-dependent behavior in rodents known as the cutaneus trunci muscle (CTM) reflex. This reflex is observed as a contraction of the skin of the back in response to tactile stimulation. Here, we confirm and extend these preliminary observations. A severe compression/contusion injury to the exposed thoracic spinal cord of the guinea pig was performed between thoracic vertebrae 10 and 11. Approximately 7 h later, a topical application of PEG was made to the injury (dura removed) for 2 min in 15 experimental animals, and levels of recovery were compared with those of 13 vehicle-treated control animals. In PEG-treated animals, 93 % recovered variable levels of CTM functioning and all recovered some level of conduction through the lesion, as measured by evoked potential techniques. The recovered reflex was relatively normal compared with the quantitative characteristics of the reflex prior to injury with respect to the direction, distance and velocity of skin contraction. Only 23 % of the control population showed any spontaneous CTM recovery (P=0.0003) and none recovered conduction through the lesion during the 1 month period of observation (P=0.0001). These results suggest that repair of nerve membranes by polymeric sealing can provide a novel means for the rapid restoration of function following spinal cord injury.