gebhart/patrepeval huggingface dataset:
Reduced expression of Dicer associated with poor prognosis in lung cancer patients (2005)

Emerging evidence suggests that microRNA, which are well-conserved, abundant and small regulatory RNA, may be involved in the pathogenesis of human cancers. We recently reported that expression of let-7 was frequently reduced in lung cancers, and that reduced let-7 expression was significantly associated with shorter patient survival. Two members of the double-stranded RNA-specific endonuclease family, Dicer and Drosha, convert precursor forms of microRNA into their mature forms using a stepwise process. In the present study, we examined expression levels of these genes in 67 non-small cell lung cancer cases, and found for the first time that Dicer expression levels were reduced in a fraction of lung cancers with a significant prognostic impact on the survival of surgically treated cases. It should be noted that multivariate COX regression analysis showed that the prognostic impact of Dicer (P=0.001) appears to be independent of disease stage (P=0.001), while logistic regression analysis demonstrated that the higher incidence of reduced Dicer expression in poorly differentiated tumors remained significant even after correction for other parameters (P=0.02). Given the fundamental and multiple biological roles of Dicer in various cellular processes, our results suggest the involvement of reduced Dicer expression in the development of lung cancers, thus warranting further investigations of the underlying mechanisms, which can be expected to enhance understanding of the molecular pathogenesis of this fatal cancer.
Optimizing microneedle arrays for transdermal drug delivery: Extension to non-square distribution of microneedles (2008)

The technology of fabricating microneedle arrays to deliver high molecular weight drugs across skin in a minimally invasive manner is receiving increasing attention. Microneedle arrays with different geometries have been manufactured using materials such as glass, polymer, metal, etc. However, a framework that can identify the optimum designs of these arrays seems to be lacking. This is important since by optimizing the microneedles dimensions (e.g., surface area of the patch, microneedle radius, etc.) the permeability of drugs in skin can be increased. To address this issue, this study presents an optimization framework for transdermal delivery of high molecular weight drug from microneedle. The optimization process is based on determining an optimization function (g) for various microneedles patterns (e.g., square, diamond, triangular, etc.). We argue that higher the value of g is the higher the drug permeability in skin is. The outputs of the developed framework have allowed us to identify the optimum design of both solid and hollow microneedles. In particular, the results have been used to predict skin permeability of high molecular weight using microneedle system. Also, optimum designs based on different classifications of skin thickness (e.g., race, age, etc.) for transdermal delivery of drugs are suggested.
Concurrency and Privacy with Payment-Channel Networks (2017)

Permissionless blockchains protocols such as Bitcoin are inherently limited in transaction throughput and latency. Current efforts to address this key issue focus on off-chain payment channels that can be combined in a Payment-Channel Network (PCN) to enable an unlimited number of payments without requiring to access the blockchain other than to register the initial and final capacity of each channel. While this approach paves the way for low latency and high throughput of payments, its deployment in practice raises several privacy concerns as well as technical challenges related to the inherently concurrent nature of payments that have not been sufficiently studied so far. In this work, we lay the foundations for privacy and concurrency in PCNs, presenting a formal definition in the Universal Composability framework as well as practical and provably secure solutions. In particular, we present Fulgor and Rayo. Fulgor is the first payment protocol for PCNs that provides provable privacy guarantees for PCNs and is fully compatible with the Bitcoin scripting system. However, Fulgor is a blocking protocol and therefore prone to deadlocks of concurrent payments as in currently available PCNs. Instead, Rayo is the first protocol for PCNs that enforces non-blocking progress (i.e., at least one of the concurrent payments terminates). We show through a new impossibility result that non-blocking progress necessarily comes at the cost of weaker privacy. At the core of Fulgor and Rayo is Multi-Hop HTLC, a new smart contract, compatible with the Bitcoin scripting system, that provides conditional payments while reducing running time and communication overhead with respect to previous approaches. Our performance evaluation of Fulgor and Rayo shows that a payment with 10 intermediate users takes as few as 5 seconds, thereby demonstrating their feasibility to be deployed in practice.
The CXCR4 chemokine receptor in acute and chronic leukaemia: a marrow homing receptor and potential therapeutic target (2007)

Chemokine (C-X-C motif) receptor 4 (CXCR4) is essential for homing and maintenance of haematopoietic stem cells in distinct stromal cell niches within the marrow. Chemotactic responsiveness of haematopoietic stem cells is restricted to the ligand for CXCR4, stromal cell-derived factor-1 (SDF-1/CXCL12), which is constitutively secreted by marrow stromal cells. Myeloid and lymphoid leukaemia cells also express CXCR4 that induces leukaemia cell chemotaxis and migration beneath marrow stromal cells. CXCR4 expression levels have a major prognostic impact in acute myeloid leukaemia. There is growing in vitro and in vivo evidence that CXCR4 expression by leukaemia cells allows for homing and their retention within the marrow. As such, leukaemia cells appear to utilise CXCR4 to access niches that are normally restricted to progenitor cells, and thereby reside in a microenvironment that favours their growth and survival. CXCR4- and integrin-mediated contact between leukaemia cells and stromal cells protects leukaemia cells from spontaneous and chemotherapy-induced cell death and therefore may represent a mechanism to explain minimal residual disease and subsequent relapses commonly seen in the treatment of these diseases. This review summarises our current knowledge regarding the importance of CXCR4 in acute and chronic leukaemia, discusses the importance of CXCR4 detection by flow cytometry in the diagnostic workup of leukaemia patients, and introduces the potential role of CXCR4-targeting compounds for the treatment of leukaemia patients.
Efficient triple helix formation by oligodeoxyribonucleotides containing alpha- or beta-2-amino-5-(2-deoxy-D-ribofuranosyl) pyridine residues (1996)

Triple helices containing C+xGxC triplets are destabilised at physiological pH due to the requirement for base protonation of 2'-deoxycytidine (dC), which has a pKa of 4.3. The C nucleoside 2-amino-5-(2'-deoxy-beta-D-ribofuranosyl)pyridine (beta-AP) is structurally analogous to dC but is considerably more basic, with a pKa of 5.93. We have synthesised 5'-psoralen linked oligodeoxyribonucleotides (ODNs) containing thymidine (dT) and either beta-AP or its alpha-anomer (alpha-AP) and have assessed their ability to form triplexes with a double-stranded target derived from standard deoxynucleotides (i.e. beta-anomers). Third strand ODNs derived from dT and beta-AP were found to have considerably higher binding affinities for the target than the corresponding ODNs derived from dT and either dC or 5-methyl-2'-deoxycytidine (5-Me-dC). ODNs containing dT and alpha-AP also showed enhanced triplex formation with the duplex target and, in addition are more stable in serum-containing medium than standard oligopyrimidine-derived ODNs or ODNs derived from dT and beta-AP. Molecular modelling studies showed that an alpha-anomeric AP nucleotide can be accommodated within an otherwise beta-anomeric triplex with only minor perturbation of the triplex structure. Molecular dynamics (MD) simulations on triplexes containing either the alpha- or beta-anomer of (N1-protonated) AP showed that in both cases the base retained two standard hydrogen bonds to its associated guanine when the 'A-type' model of the triplex was used as the start-point for the simulation, but that bifurcated hydrogen bonds resulted when the alternative 'B-type' triplex model was used. The lack of a differential stability between alpha-AP- and beta-AP-containing triplexes at pH >7, predicted from the behaviour of the B-type models, suggests that the A-type models are more appropriate.
Criteria for a Clinically Informative Serum Biomarker in Acute Ischaemic Stroke: A Review of S100B (2009)

The evidence suggests that S100B is not a valuable biomarker for diagnosing acute ischaemic stroke. Instead, it may have a more promising role in non-specialist hospitals, as an additional tool for identifying patients at increased risk of specific early neurological complications after stroke and as a surrogate marker of cerebral damage and functional outcome, particularly in a research setting.
Growth, sucrose synthase, and invertase activities of developing Phaseolus vulgaris L. fruits (1994)

ABSTRACT Activities of the sucrose‐cleaving enzymes, acid and neutral invertase and sucrose synthase, were measured in pods and seeds of developing snap bean ( Phaseolus vulgaris L.) fruits, and compared with 14 C‐import, elongation and dry weight accumulation. During the first 10 d post‐anthesis, pods elongated rapidly with pod dry weight increase lagging behind by several days. The temporal patterns of acid invertase activity and import coincided closely during the first part of pod development, consonant with a central role for this enzyme in converting imported sucrose during pod elongation and early dry weight accumulation. Later, sucrose synthase became the predominant enzyme of dry weight accumulation and was possibly associated with the development of phloem in pod walls. Sucrose synthase activity in seeds showed two peaks, corresponding to two phases of rapid import and dry weight accumulation; hence, sucrose synthase was associated with seed sink growth. Acid invertase activities in seeds were low and did not show a noticeable relationship with import or growth. All neutral invertase activities, during pod and seed development, were too low for it to have a dominant role in sucrose cleavage. Changes in activities of certain sucrose‐cleaving enzymes appear to be correlated with certain sink functions, including import, storage of reserves, and biosynthetic activities. The data supports the association of specific sucrose‐cleaving enzymes with the specific processes that occur in the developing pods and seeds of snap bean fruits; for example, acid invertase with pod elongation and sucrose synthase with fruit dry matter accumulation.
A Commentary on the Innovation of China's Lifelong Education Theory (2011)

With the recent establishment of China's lifelong education system, a new era has begun in terms of innovation in lifelong education theory and its actual implementation. This paper studies and analyzes the innovation of lifelong education theory in the National Plan for Medium and Long-term Education Reform and Development (2010-2020). According to the National Plan, the innovative theory of lifelong education is presented in five aspects: (1) innovation in education theory and practice in building a comprehensive framework for lifelong education; (2) innovation in regards to society's expectations of public education in the lifelong education spectrum; (3) innovation of lifelong education to meet diversified public demands in terms of spiritual, physical, and material aspects; (4) innovation in changing the traditional teaching and learning approaches in lifelong education; and (5) innovation in building an education-based system that facilitates social communication and formation of lifelong education objectives in a learning society. This paper highlights the objectives of the construction of the lifelong education system: to provide education opportunities for all; to promote people's all-round development; and to enhance citizens' quality.
Estimation and removal of clock skew from network delay measurements (1999)

Packet delay and loss traces are frequently used by network engineers, as well as network applications, to analyze network performance. The clocks on the end-systems used to measure the delays, however, are not always synchronized, and this lack of synchronization reduces the accuracy of these measurements. Therefore, estimating and removing relative skews and offsets from delay measurements between sender and receiver clocks are critical to the accurate assessment and analysis of network performance. We introduce a linear programming-based algorithm to estimate the clock skew in network delay measurements and compare it with three other algorithms. We show that our algorithm has a time complexity of O(N), leaves the delay after the skew removal positive, and is robust in the sense that the error margin of the skew estimate is independent of the magnitude of the skew. We use traces of real Internet delay measurements to assess the algorithm, and compare its performance to that of three other algorithms. Furthermore, we show through simulation that our algorithm is unbiased, and that the sample variance of the skew estimate is better (smaller) than existing algorithms.
Membrane Permeabilization by Small Hydrophobic Nonstructural Proteins of Japanese Encephalitis Virus (1999)

Infection with Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, may cause acute encephalitis in humans and induce severe cytopathic effects in various types of cultured cells. We observed that JEV replication rendered infected baby hamster kidney (BHK-21) cells sensitive to the translational inhibitor hygromycin B or alpha-sarcine, to which mock-infected cells were insensitive. However, little is known about whether any JEV nonstructural (NS) proteins contribute to virus-induced changes in membrane permeability. Using an inducible Escherichia coli system, we investigated which parts of JEV NS1 to NS4 are capable of modifying membrane penetrability. We found that overexpression of NS2B-NS3, the JEV protease, permeabilized bacterial cells to hygromycin B whereas NS1 expression failed to do so. When expressed separately, NS2B alone, but not NS3, was sufficient to alter bacterial membrane permeability. Similarly, expression of NS4A or NS4B also rendered bacteria susceptible to hygromycin B inhibition. Examination of the effect of NS1 to NS4 expression on bacterial growth rate showed that NS2B exhibited the greatest inhibitory capability, followed by a modest repression from NS2A and NS4A, whereas NS1, NS3, and NS4B had only trivial influence with respect to the vector control. Furthermore, when cotransfected with a reporter gene luciferase or beta-galactosidase, transient expression of NS2A, NS2B, and NS4B markedly reduced the reporter activity in BHK-21 cells. Together, our results suggest that upon JEV infection, these four small hydrophobic NS proteins have various modification effects on host cell membrane permeability, thereby contributing in part to virus-induced cytopathic effects in infected cells.
Assessment and Management of Foot Disease in Patients with Diabetes (1994)

Limb- or life-threatening complications in patients with diabetes can be prevented with an integrated, multidisciplinary approach. Most patients seen in clinical practice are in the early stages of the disease process. Glycemic control retards the progression of neuropathy, which is the most important risk factor for ulceration. Early detection of the loss of protective sensation and implementation of strategies to prevent ulceration will reduce the rates of limb-threatening complications. Clinicians should routinely examine the feet of diabetic patients. Education in foot care, proper footwear, and close follow-up are required to prevent or promptly detect neuropathic injury. If ulceration occurs, removal of pressure from the site of the ulcer and careful management of the wound will allow healing in most cases. The failure to heal despite these measures should prompt a search for associated arterial insufficiency. If infection is present, appropriate antimicrobial therapy combined with immediate surgical intervention, including revascularization when necessary, will increase the chances of saving the limb. With this comprehensive approach, it is possible to achieve the goal of a 40 percent decrease in amputation rates among diabetic patients by the year 2000.
Medullary pain facilitating neurons mediate allodynia in headache‐related pain (2009)

Facial and hind-paw allodynia associated with dural stimulation is a useful surrogate of pain associated with primary headache including migraine and may be exploited mechanistically for development of novel therapeutic strategies for headache pain. The data also demonstrate the requirement for activation of descending facilitation from the RVM for the expression of cranial and extracranial cutaneous allodynia, and are consistent with a brainstem generator of allodynia associated with headache disorders.
Heparan sulfate proteoglycans are essential for FGF receptor signaling during Drosophila embryonic development (1999)

The Drosophila sugarless and sulfateless genes encode enzymes required for the biosynthesis of heparan sulfate glycosaminoglycans. Biochemical studies have shown that heparan sulfate glycosaminoglycans are involved in signaling by fibroblast growth factor receptors, but evidence for such a requirement in an intact organism has not been available. We now demonstrate that sugarless and sulfateless mutant embryos have phenotypes similar to those lacking the functions of two Drosophila fibroblast growth factor receptors, Heartless and Breathless. Moreover, both Heartless- and Breathless-dependent MAPK activation is significantly reduced in embryos which fail to synthesize heparan sulfate glycosaminoglycans. Consistent with an involvement of Sulfateless and Sugarless in fibroblast growth factor receptor signaling, a constitutively activated form of Heartless partially rescues sugarless and sulfateless mutants, and dosage-sensitive interactions occur between heartless and the heparan sulfate glycosaminoglycan biosynthetic enzyme genes. We also find that overexpression of Branchless, the Breathless ligand, can partially overcome the requirement of Sugarless and Sulfateless for Breathless activity. These results provide the first genetic evidence that heparan sulfate glycosaminoglycans are essential for fibroblast growth factor receptor signaling in a well defined developmental context, and support a model in which heparan sulfate glycosaminoglycans facilitate fibroblast growth factor ligand and/or ligand-receptor oligomerization.
Protective Effect of C1 Esterase Inhibitor on Reperfusion Injury in the Rat Middle Cerebral Artery Occlusion Model (2003)

The results of this study indicated that C1-INH reduced polymorphonuclear leukocyte accumulation and neuronal damage in focal ischemia and reperfusion.
Dynamic holography for optical interconnections II Routing holograms with predictable location and intensity of each diffraction order (2001)

An analysis of dynamic phase-only holograms, described by fractional notation and recorded onto a pixelated spatial light modulator (SLM) in a reconfigurable optical beam-steering switch, is presented. The phase quantization and arrangement of the phase states and the SLM pixelation and dead-space effects are decoupled, expressed analytically, and simulated numerically. The phase analysis with a skip-rotate rule reveals the location and intensity of each diffraction order at the digital replay stage. The optical reconstruction of the holograms recorded onto SLM's with rectangular pixel apertures entails sinc-squared scaling, which further reduces the intensity of each diffraction order. With these two factors taken into account, the highest values of the nonuniform first-order diffraction efficiencies are expected to be 33%, 66%, and 77% for two-, four-, and and eight-level one-dimensional holograms with a 90% linear pixel fill factor. The variation of the first-order diffraction efficiency and the relative replay intensities were verified to within 1 dB by performing the optical reconstruction of binary phase-only holograms recorded onto a ferroelectric liquid crystal on a silicon SLM.
Neural Tissue Formation Within Porous Hydrogels Implanted in Brain and Spinal Cord Lesions: Ultrastructural, Immunohistochemical, and Diffusion Studies (1999)

A biocompatible heterogeneous hydrogel of poly [N-(2-hydroxypropyl) methacrylamide] (PHPMA), was evaluated for its ability to promote tissue repair and enhance axonal regrowth across lesion cavities in the brain and spinal cord in adult and juvenile (P17 P21) rats. Incorporation of PHPMA hydrogels into surrounding host tissue was examined at the ultrastructural level and using immunohistochemical techniques. In addition, and in parallel to these studies, diffusion parameters (volume fraction and tortuosity of the gel network) of the PHPMA hydrogels were evaluated pre- to postimplantation using an in vivo real-time iontophoretic method. The polymer hydrogels were able to bridge tissue defects created in the brain or spinal cord, and supported cellular ingrowth, angiogenesis, and axonogenesis within the structure of the polymer network. As a result, a reparative tissue grew within the porous structure of the gel, composed of glial cells, blood vessels, axons and dendrites, and extracellular biological matrices, such as laminin and/or collagen. Consistent with matrix deposition and tissue formation within the porous structure of the PHPMA hydrogels, there were measurable changes in the diffusion characteristics of the polymers. Extracellular space volume decreased and tortuosity increased within implanted hydrogels, attaining values similar to that seen in developing neural tissue. PHPMA polymer hydrogel matrices thus show neuroinductive and neuroconductive properties. They have the potential to repair tissue defects in the central nervous system by replacing lost tissue and by promoting the formation of a histotypic tissue matrix that facilitates and supports regenerative axonal growth. () ()
Scheduling in the Z-Polyhedral Model (2007)

The polyhedral model is extensively used for analyses and transformations of regular loop programs, one of the most important being automatic parallelization. The model, however, is limited in expressivity and the need for the generalization to more general class of programs has been widely known. Analyses and transformations in the polyhedral model rely on certain closure properties. Recently, these closure properties were extended to programs where variables may be defined over unions of Z-polyhedra which are the intersection of polyhedra and lattices. We present the scheduling analysis for the automatic parallelization of programs in the Z-polyhedral model, and obtain multidimensional schedules through an ILP formulation that minimizes latency. The resultant schedule can then be used to construct a space-time transformation to obtain an equivalent program in the Z-polyhedral model.