gebhart/patrepeval huggingface dataset:
Therapy-related myelodysplasia and acute myeloid leukemia. Cytogenetic characteristics of 115 consecutive cases and risk in seven cohorts of patients treated intensively for malignant diseases in the Copenhagen series. (1993)

Therapy-related acute myeloid leukemia (t-AML), often presenting as myelodysplasia (t-MDS), has become the most serious long-term complication of cancer therapy and offers a unique opportunity to study chemical leukemogenesis. Seven cohorts of patients treated for six different types of primary tumor have been followed closely for leukemic complications, and 115 consecutive patients with t-MDS or t-AML, including 45 cases from the cohorts, have been investigated cytogenetically at our institutions during the past 16 years. In patients primarily treated with alkylating agents, the risk of t-MDS and t-AML increased by approximately 1% per year from 2 to at least 8 years after start of treatment. In most cases, the disease presented as t-MDS with loss of a whole chromosome 5 or 7, or various parts of their long arms, and the leukemias were of FAB-subtypes M1, M2, or M4. In patients treated with drugs targeting at DNA-topoisomerase II, such as etoposide, doxorubicin, 4-epidoxorubicin, or mitoxantrone combined with drugs reacting directly with DNA, such as cisplatin or alkylating agents, the risk of leukemia increased much more steeply from only one year after start of therapy. These early onset cases often presented as overt leukemia of FAB-subtypes M4 or M5 with balanced translocations to chromosome bands 11q23 and 21q22, whereas later onset cases often shared characteristics with cases observed after therapy with alkylating agents alone. Both alkylation of DNA and poisoning of DNA-topoisomerase II may result in development of t-AML with different clinical and cytogenetic characteristics. There may be a synergistic leukemogenic effect between the two types of drug, and in patients with germ cell tumors treated with etoposide, cisplatin and bleomycin, reassessment suggested the risk of leukemia to increase exponentially with increasing doses of cisplatin and etoposide.
Deep belief nets for natural language call-routing (2011)

This paper considers application of Deep Belief Nets (DBNs) to natural language call routing. DBNs have been successfully applied to a number of tasks, including image, audio and speech classification, thanks to the recent discovery of an efficient learning technique. DBNs learn a multi-layer generative model from unlabeled data and the features discovered by this model are then used to initialize a feed-forward neural network which is fine-tuned with backpropagation. We compare a DBN-initialized neural network to three widely used text classification algorithms; Support Vector machines (SVM), Boosting and Maximum Entropy (MaxEnt). The DBN-based model gives a call-routing classification accuracy that is equal to the best of the other models even though it currently uses an impoverished representation of the input.
Muscle recruitment through electrical stimulation of the lumbo-sacral spinal cord (2000)

The goal of this study was to determine the feasibility of producing graded muscle contraction in individual muscles or muscle groups by electrically stimulating motor neurons in the lumbo-sacral spinal cord. Recruitment curves were obtained for quadriceps, tibialis anterior and triceps surae/plantaris by stimulating their activation pools in the ventral horn of the feline spinal cord. Mean twitch times-to-peak for quadriceps, tibialis anterior and triceps surae/plantaris were 33.0, 41.0, and 36.0 ms, respectively. Twitch duration as a function of stimulus strength demonstrated a mixed motor unit recruitment order, distinctively different from the inverse recruitment order exhibited by conventional methods of electrical stimulation of peripheral nerve. The recruitment curve slopes (expressed as a percentage of maximum force per nanocurrent of delivered charge) were shallow: 7.9 for quadriceps, 2.6 for tibialis anterior and 8.5 for triceps surae/plantaris. These results show that graded control of force in individual muscles or muscle groups can be obtained through spinal cord stimulation, and suggest that spinal cord stimulation could be used for functional neuromuscular stimulation applications.
Expression of the Pseudomonas syringae avirulence protein AvrB in plant cells alleviates its dependence on the hypersensitive response and pathogenicity (Hrp) secretion system in eliciting genotype-specific hypersensitive cell death. (1996)

The nonpathogenic bacteria Pseudomonas fluorescens and Escherichia coli can elicit a genotype-specific hypersensitive response (HR) in plants if they express both the HR and pathogenesis (Hrp) protein secretion system and the HrpZ harpin from P. syringae pv syringae 61 and a P. syringae avirulence (avr) gene whose presence is recognized by a corresponding disease resistance gene in the plant. We have found that the recognition event appears to require transfer of the Avr protein into the plant cell. Elicitation of a genotype-specific HR was observed with avrB+ P. fluorescens in soybean and Arabidopsis plants carrying resistance genes RPG1 and RPM1, respectively, and with avrPto+ E. coll in tomato plants carrying resistance gene PTO, but only if the Hrp secretion system, HrpZ, and the appropriate Avr proteins were produced in the same bacterial cell. The failure of avrB hyperexpression and exogenous AvrB or HrpZ to alleviate these requirements in soybean and Arabidopsis suggests that the site of AvrB action is not in the bacterial cell or plant apoplast. An Arabidopsis rps3 (rpm1) glabrous1 mutant was transformed with constructs expressing avrB and was crossed with an Arabidopsis ecotype Columbia (RPM1 GLABROUS1) plant. F1 seedlings (identified by their kanamycin-resistant, pubescent phenotype) exhibited extensive necrosis on cotyledon leaves 10 days postgermination. Ecotype Columbia and rps3-1 leaves biolistically cobombarded with plasmids expressing the beta-glucuronidase (GUS) gene and avrB failed to produce GUS activity (indicative of cell death) only when RPM1 and avrB were present in the leaf. Thus, both stable and transient expression of avrB in Arabidopsis resulted in RPM1-dependent necrosis, and the only demonstrable site of action for AvrB was inside plant cells.
Friction modeling in concentric tube robots (2011)

Concentric tube robots are a novel class of continuum robots that are constructed by combining pre-curved elastic tubes such that the overall shape of the robot is a function of the relative rotations and translations of the constituent tubes. Frictionless kinematic and quasistatic force models for this class of robots have been developed that incorporate bending and twisting of the tubes. Experimental evaluation of these models has revealed, however, a directional dependence of tube rotation on robot shape that is not predicted by these models. To explain this behavior, this paper models the contributions of friction arising from two sources: the distributed forces of contact between the tubes along their length and the concentrated bending moments generated at discontinuities in curvature and at the boundaries. It is shown that while friction due to distributed forces is insufficient to explain the experimentally observed tube twisting, a simple model of frictional torque arising from concentrated moments provides a good match with the experimental data.
Inhibitors of basement membrane collagen synthesis prevent endothelial cell alignment in matrigel in vitro and angiogenesis in vivo. (1994)

These results indicate that newly synthesised collagen is a prerequisite for expression of the endothelial cell phenotype for tube formation and that prevention of collagenous protein biosynthesis inhibits tube formation and angiogenesis in vivo.
Anti-infective effect of poly-beta 1-6-glucotriosyl-beta 1-3-glucopyranose glucan in vivo (1992)

Mice challenged with Escherichia coli or Staphylococcus aureus were protected against lethal peritonitis by the intravenous administration of 10 micrograms of poly-beta 1-6-glucotriosyl-beta 1-3-glucopyranose (PGG) glucan per animal 4 to 6 h prior to bacterial challenge. Subsequent studies with the rat model for intra-abdominal sepsis indicated that intramuscular doses of 10 to 100 micrograms per animal 24 and 4 h prior to surgical implantation of the bacterial inoculum reduced the early mortality associated with the peritonitis phase of this experimental disease process. Quantitative cultures of blood obtained from challenged rats showed that significantly fewer organisms were present in the blood of PGG glucan-treated animals than in that of untreated animals. Quantitative studies of leukocytes of rats and mice following a single injection of PGG glucan showed a modest transient increase in the total leukocyte count. The possible mechanisms by which protection occurs in the animal model system are discussed.
DANGEROUS DRIVERS' BEHAVIOR IN ROAD TRAFFIC - REASONS, REASULTS, PREVENTION (2008)

Driving a car is a task demanding particular competencies, which include: knowledge, skills and specific personality and mental traits. Every driver should posses: knowledge about traffic law regulations, practical skills of driving a vehicle, ability to predict traffic situations and, what is especially important, self-diagnosis ability. Those skills determine driving safety. Paper presents dangerous and aggressive driving behaviour on the roads. It describes characteristic features of drivers and type of offenses committed by them, as well as recognition of the scale and reasons for aggression in the road traffic. Paper includes detailed research results analyses of aggressive behaviour and its evaluation by road traffic controllers - police (408 persons), and by drivers participating in the demerit points reduction scheme (504 persons). Survey results indicate that drivers consciously break traffic law, underestimate danger, overestimate their own abilities, feel unpunished and they don’t know traffic regulations well. All results shows that aggression is a frequent problem, especially concerning 18-39 year old group with wrong attitudes towards others road users. Importance of psychological testing of drivers, necessity of psycho-educational and preventive actions was pointed out in view of these circumstances. Research has allowed determining psychological reasons of the drivers’ attitude and behaviour. Conclusions suggest undertaking activities and campaigns whose purpose is to change dangerous attitudes and habits and create re-education systems for the drivers who regularly break road traffic regulations.
Discovering Natural Product Modulators to Overcome Multidrug Resistance in Cancer Chemotherapy (2011)

Multidrug resistance caused by the overexpression of ABC drug transporters is a major obstacle in clinical cancer chemotherapy. For several years, it appeared that direct inhibition of ABC transporters would be the cheapest and most efficient way to combat this problem. Unfortunately, progress in finding a potent, selective inhibitor to modulate ABC transporters and restore drug sensitivity in multidrug-resistant cancer cells has been slow and challenging. Candidate drugs should ideally be selective, potent and relatively non-toxic. Many researchers in recent years have turned their attention to utilizing natural products as the building blocks for the development of the next generation of inhibitors, especially after the disappointing results obtained from inhibitors of the first three generations at the clinical trial stage. The first step is to discover natural substances (distinct from the first three generation inhibitors) that are potent, selective and relatively non-toxic in order to be used clinically. Here, we present a brief overview of the prospect of using natural products to modulate the function of ABC drug transporters clinically and their impact on human physiology and pharmacology.
Dynamic sleep transistor and body bias for active leakage power control of microprocessors (2003)

In order to manage the active power consumption of high-performance digital designs, active leakage control techniques are required to provide significant leakage power savings coupled with fast time constants for entering and exiting idle mode. In this paper, dynamic sleep transistors and body bias are used in conjunction with clock gating to control active leakage for a 32-bit integer execution core in 130-nm CMOS technology. Measurements on pMOS sleep transistor reveal that lowest-leakage state is reached in less than 1 μs, resulting in 37× reduction in leakage power, while reactivation of block is achieved in less than two clock cycles. PMOS body bias reduces leakage power by 2× with no performance penalty, and similar reactivation time. Power measurements at 4 GHz, 1.3 V, 75°C demonstrate 8% total power reduction using dynamic body bias and 15% power reduction using a pMOS sleep transistor, for a typical activity profile.
RORing T cells target CLL and MCL (2010)

Genetically targeted T lymphocytes are emerging as powerful antitumor agents. Their rapid generation, made possible by robust and clinically applicable gene transfer technologies, provides a novel means to circumvent immune tolerance and generate tumor-reactive T cells on demand. Thus, patient peripheral blood T cells can be readily redirected toward any chosen antigen, including tumor antigens which are for the most part “self” antigens, and infused to promptly raise the number of tumor-reactive T cells without requiring active immunization and without the risk of deleterious alloreactivity (as may be the case after donor leukocyte infusion or non-T cell–depleted bone marrow transplantation).
The effectiveness of non-invasive complementary therapies in reducing postoperative nausea and vomiting following abdominal laparoscopic surgery in women: a systematic review (2009)

There is sufficient evidence to suggest that several of the interventions assessed could play a role in a multimodal approach to minimise PONV following abdominal laparoscopic surgery, albeit requiring further research to confirm that promise. The two interventions of note are the use of the Korean Hand acupoints for prophylactic purposes, particularly acupressure applied to the acupoint K-K9, and the use of impregnated pads for the inhalation of 70% isopropyl alcohol to treat established nausea in females. There is also some evidence to suggest that acupressure or acustimulation at P6 may be effective in reducing nausea and vomiting in patients (females and males) having a laparoscopic cholecystectomy.
Present and Future of Adeno Associated Virus Based Gene Therapy Approaches (2012)

During the last 20 years, transgenic constructs based on adeno associated virus (AAV) have been tested in disease models and proved their efficacy to revert a wide range of pathologies without major side effects. Based on these results, up to 20 clinical trials have been set up to prove therapeutic effect of AAV vectors on neurodegenerative diseases, retinopathies and neuromuscular diseases, among others. It has been shown that AAV vectors support localized long-term, gene expression in the central nervous system, and that restoration of visual function can be achieved in Leber's congenital amaurosis retinopathy. The clinical trials also highlighted new challenges for AAV mediated gene transfer, such as the circumvention of T-cell response to transduced cells. Currently, miniaturized and codon-optimized transgenes, exon skipping cassettes, novel tissue-specific promoters and vector chimeras with tissue-selective tropism are being tested to improve the efficiency and safety of transgene delivery, as required to meet pharmaceutical industry standards. The aim of this review is to revise the latest patents and news on AAV vectors, in order to summarize the state of the art and the potential issues that still need to be faced by pharmaceutical companies for successful gene transfer and commercialization of AAV-based drugs.
The expanding role of cisplatin in the treatment of non-small-cell lung cancer. (1989)

Cisplatin has been employed in the treatment of non-small-cell lung cancer (NSCLC) since the late 1970s. Current evidence suggests that it may be the most effective single drug for the treatment of NSCLC patients. The overall response rate as a single agent is 21%, though responses are higher in previously untreated patients given high doses. Cisplatin combinations are the most effective therapy for advanced NSCLC. Two-drug combinations with a vinca alkaloid or etoposide consistently provide the best overall survival with acceptable toxicity. These two-drug combinations improve survival by 7 to 17 weeks compared with no chemotherapy. Cisplatin-based combinations improved survival by a greater degree in locally advanced patients (Stages IIIA and IIIB) when given with chest radiotherapy. There is evidence that cisplatin-based combinations also prolong survival when given after surgery for resected stage II and IIIA patients. In summary, cisplatin-based chemotherapy regimens are the preferred systemic therapy for NSCLC patients and prolong survival to a small degree.
N-Glycan Modification in Aspergillus Species (2007)

The production by filamentous fungi of therapeutic glycoproteins intended for use in mammals is held back by the inherent difference in protein N-glycosylation and by the inability of the fungal cell to modify proteins with mammalian glycosylation structures. Here, we report protein N-glycan engineering in two Aspergillus species. We functionally expressed in the fungal hosts heterologous chimeric fusion proteins containing different localization peptides and catalytic domains. This strategy allowed the isolation of a strain with a functional alpha-1,2-mannosidase producing increased amounts of N-glycans of the Man5GlcNAc2 type. This strain was further engineered by the introduction of a functional GlcNAc transferase I construct yielding GlcNAcMan5GlcNac2 N-glycans. Additionally, we deleted algC genes coding for an enzyme involved in an early step of the fungal glycosylation pathway yielding Man3GlcNAc2 N-glycans. This modification of fungal glycosylation is a step toward the ability to produce humanized complex N-glycans on therapeutic proteins in filamentous fungi.
Amplified and rearranged epidermal growth factor receptor genes in human glioblastomas reveal deletions of sequences encoding portions of the N- and/or C-terminal tails. (1992)

This study describes genomic rearrangements near the 3' end of the epidermal growth factor receptor (EGFR) gene in eight glioblastomas displaying coamplification and expression of both normal and rearranged EGFR. In four of these cases, it was possible by PCR to amplify tumor EGFR cDNA, which allowed sequence determination of the 3' transcript alterations associated with the rearrangements. Such analysis revealed that the four cases have in common a deletion of 255 bases that encode a portion of the receptor's cytoplasmic domain. The remaining four cases revealed genomic rearrangements in the same region of the gene as those described above and revealed aberrant EGFR transcripts lacking the same 255 bases determined to be missing in the sequenced EGFR cDNAs as well as large regions of contiguous downstream sequences. Therefore, all of the eight cases described here express transcripts that do not encode large C-terminal, intracellular portions of the receptor. In three of the eight cases, the EGFR transcripts displaying a 3' alteration also displayed a 5' inframe deletion of sequences encoding a portion of the extracellular domain, and for one of the corresponding patients it was possible to determine that the two transcript alterations were acquired as separate events. We have now detected the 5' and/or 3' alterations in 21 of 32 cases of glioblastoma with EGFR amplification; no genetic alterations have been detected in glioblastomas without EGFR amplification. In combination with previously published reports, these data suggest the in vivo evolution of EGFR toward an increasingly oncogenic potential through gene amplification with subsequent and successive gene alterations.
Facet-Free Si Selective Epitaxial Growth Adaptable to Elevated Source/Drain MOSFETs with Narrow Shallow Trench Isolation (1999)

A novel selective epitaxial growth (SEG) process that realizes a facet-free elevated source/drain (S/D) is proposed. The key points are the appropriate selection of the gate-sidewall material and its structural improvement. It was observed that the facet was not formed adjacent to SiN in contrast to the SiO 2 case. Therefore, SiN is selected as a gate-sidewall. The novel gate-sidewall is constructed from a SiN sidewall and SiO 2 liner layer which acts as a sidewall reactive ion etching (RIE) stopper. The SiO 2 liner layer is lateral etched by wet treatment. By the SEG process, the facet, which is formed adjacent to the SiO 2 liner is screened out within the lateral etched region, and no facet is observed along the SiN sidewall. Si lateral overgrowth on the shallow trench isolation (STI) region was also confirmed to be controllable in the facet-free SEG process. This novel SEG process was found to be successfully adapted to facet-free elevated S/D.
Enhanced cyclophosphamide and ifosfamide activation in primary human hepatocyte cultures: response to cytochrome P-450 inducers and autoinduction by oxazaphosphorines. (1997)

The anticancer oxazaphosphorine prodrugs cyclophosphamide and ifosfamide are activated in human liver by a 4-hydroxylation reaction catalyzed by multiple cytochrome P450 (CYP) enzymes. In the present study, we used a cultured human hepatocyte model to identify possible inducers of the CYP-catalyzed activation of these two anticancer prodrugs. Treatment of primary cultures of human hepatocytes with phenobarbital, dexamethasone, or rifampin elevated hepatocyte microsomal oxazaphosphorine 4-hydroxylation by up to 200-400% of control for both drug substrates. These inductions were associated with corresponding increases in immunoreactive CYP2B6, CYP2C8, CYP2C9, and CYP3A4, all previously shown to catalyze oxazaphosphorine activation. Rifampin (1 microM, 96-h exposure) was a particularly potent inducer of ifosfamide and cyclophosphamide 4-hydroxylation, as well as of CYP3A protein levels and CYP3A-dependent testosterone 6beta-hydroxylation. CYP3A4, CYP2C8, and CYP2C9 protein levels were also increased by exposure of the hepatocytes to cyclophosphamide or ifosfamide (50 microM), which thereby enhanced their own rates of 4-hydroxylation in the cultured hepatocytes. In one human hepatocyte culture that contained the polymorphically expressed CYP3A5 in addition to the more widely expressed CYP3A4, only CYP3A4 was induced by cyclophosphamide, ifosfamide, and rifampin. These studies: (a) demonstrate an underlying metabolic basis for the clinically important oxazaphosphorine autoinduction pharmacokinetics seen with these drugs in cancer patients; and (b) identify rifampin and other CYP inducers as potentially useful for increasing the rates of cyclophosphamide 4-hydroxylation and ifosfamide 4-hydroxylation in human liver in a manner that could favorably impact the clinical pharmacokinetics of these anticancer prodrugs.
Condition monitoring of wind turbines based on amplitude demodulation (2010)

Wind energy conversion systems (WECS) have become a focal point in the research of renewable energy sources. In order to make wind turbine reliable and competitive, it is important to reduce the operational and maintenance costs. The most efficient way to reduce it relies on condition monitoring and fault diagnostics. This paper proposes a new fault detector based on the amplitude demodulation of the three-phase stator current. Simulations show that this low-complexity method is well suited for stationary or non-stationary behavior.