gebhart/patrepeval huggingface dataset:
Stochastic cancer progression driven by non‐clonal chromosome aberrations (2006)

Cancer research has previously focused on the identification of specific genes and pathways responsible for cancer initiation and progression based on the prevailing viewpoint that cancer is caused by a stepwise accumulation of genetic aberrations. This viewpoint, however, is not consistent with the clinical finding that tumors display high levels of genetic heterogeneity and distinctive karyotypes. We show that chromosomal instability primarily generates stochastic karyotypic changes leading to the random progression of cancer. This was accomplished by tracing karyotypic patterns of individual cells that contained either defective genes responsible for genome integrity or were challenged by onco-proteins or carcinogens that destabilized the genome. Analysis included the tracing of patterns of karyotypic evolution during different stages of cellular immortalization. This study revealed that non-clonal chromosomal aberrations (NCCAs) (both aneuploidy and structural aberrations) and not recurrent clonal chromosomal aberrations (CCAs) are directly linked to genomic instability and karyotypic evolution. Discovery of "transitional CCAs" during in vitro immortalization clearly demonstrates that karyotypic evolution in solid tumors is not a continuous process. NCCAs and their dynamic interplay with CCAs create infinite genomic combinations leading to clonal diversity necessary for cancer cell evolution. The karyotypic chaos observed within the cell crisis stage prior to establishment of the immortalization further supports the ultimate importance of genetic aberrations at the karyotypic or genome level. Therefore, genomic instability generated NCCAs are a key driving force in cancer progression. The dynamic relationship between NCCAs and CCAs provides a mechanism underlying chromosomal based cancer evolution and could have broad clinical applications.
Label-free single-cell separation and imaging of cancer cells using an integrated microfluidic system (2017)

The incidence of cancer is increasing worldwide and metastatic disease, through the spread of circulating tumor cells (CTCs), is responsible for the majority of the cancer deaths. Accurate monitoring of CTC levels in blood provides clinical information supporting therapeutic decision making, and improved methods for CTC enumeration are asked for. Microfluidics has been extensively used for this purpose but most methods require several post-separation processing steps including concentration of the sample before analysis. This induces a high risk of sample loss of the collected rare cells. Here, an integrated system is presented that efficiently eliminates this risk by integrating label-free separation with single cell arraying of the target cell population, enabling direct on-chip tumor cell identification and enumeration. Prostate cancer cells (DU145) spiked into a sample with whole blood concentration of the peripheral blood mononuclear cell (PBMC) fraction were efficiently separated and trapped at a recovery of 76.2 ± 5.9% of the cancer cells and a minute contamination of 0.12 ± 0.04% PBMCs while simultaneously enabling a 20x volumetric concentration. This constitutes a first step towards a fully integrated system for rapid label-free separation and on-chip phenotypic characterization of circulating tumor cells from peripheral venous blood in clinical practice.
Congenital Deficiency of Vitamin K Dependent Coagulation Factors in Two Families Presents as a Genetic Defect of the Vitamin K-Epoxide-Reductase-Complex (2000)

Hereditary combined deficiency of the vitamin K dependent coagulation factors is a rare bleeding disorder. To date, only eleven families have been reported in the literature. The phenotype varies considerably with respect to bleeding tendency, response to vitamin K substitution and the presence of skeletal abnormalities, suggesting genetic heterogeneity. In only two of the reported families the cause of the disease has been elucidated as either a defect in the gamma-carboxylase enzyme (1) or in a protein of the vitamin K 2,3-epoxide reductase (VKOR) complex (2). Here we present a detailed phenotypic description of two new families with an autosomal recessive deficiency of all vitamin K dependent coagulation factors. In both families offspring had experienced severe or even fatal perinatal intracerebral haemorrhage. The affected children exhibit a mild deficiency of the vitamin K dependent coagulation factors that could be completely corrected by oral substitution of vitamin K. Sequencing and haplotype analysis excluded a defect within the gamma-carboxylase gene. The finding of highly increased amounts of vitamin K epoxide in all affected members of both families indicated a defect in a protein of the VKOR-multienzyme-complex. Further genetic analysis of such families will provide the basis for a more detailed understanding of the structure-function relation of the enzymes involved in vitamin K metabolism.
Using machine learning to predict the driving context whilst driving (2013)

This paper discusses how the driving context (driving events and distraction level) can be determined using a mobile phone equipped with several sensors. The majority of existing in-car communication systems (ICCS) available today are built-in and do not use the driving context. This creates two issues: firstly, the use of an ICCS is limited to specific cars and secondly, the driver's safety remains an issue, as the driving context is not taken into account. This paper discusses two experiments in which data are collected, trained and tested in order to create a model that predicts driving events and distraction level. A mobile, context-aware application was built using the MIMIC (Multimodal Interface for Mobile Info-communication with Context) Framework. The Inference Engine uses information from several sources, namely mobile sensors, GPS and weather information, to infer both the driving event and the distraction level. The results obtained showed that the driving events and the distraction level can be accurately predicted. The driving events were predicted using the IB1 technique with an accuracy of 92.25%. In the second experiment, the distraction level was predicted with 95.16% accuracy, using the KStar (decision tree) technique. An analysis of the decision tree showed that some variables were more important than others in predicting the driving context. These variables included the speed and direction, as well as acceleration, magnetic field and orientation.
Impact strength of high density microcellular poly(vinyl chloride) foams (2000)

Abstract The impact strength of microcellular poly(vinyl chloride) (PVC) produced from an industrial formulation was investigated. The solid‐state process with carbon dioxide as the blowing agent was used to prepare the specimens. Processing conditions were explored to produce microcellular PVC with a relative density of 0.6 and higher. These foams were impact tested by using a falling‐weight impact tester. Impact strength of microcellular PVC was found to decrease linearly with relative density. The gas saturation pressure did not significantly affect the impact strength of microcellular PVC foams. Microcellular PVC foams with up to 40% reduction in density possessed a normalized mean failure energy of 3.8 J/mm (0.85 in.‐lb/0.001 in.).
Panel Provides Peer Review of Intelligence Research (2007)

In 2002, U.S. intelligence officials claimed that the Iraqi government owned a number of mobile labs capable of producing biological weapons. After U.S.-led forces invaded Iraq, the labs were revealed to be production facilities for hydrogen used to fill weather balloons. In 2005, a government commission said the error was due to a lack of scientific expertise within the U.S. intelligence community.
The Hexokinases: Kinetic, Physical, and Regulatory Properties (1973)

Introduction Measurement of Hexokinase Activity Yeast Hexokinase Mammalian Hexokinases
Near single user performance using iterative multi-user detection for CDMA with turbo-code decoders (2002)

This paper discusses a code-division multiple access (CDMA) iterative multi-user receiver with forward error control (FEC) decoding. The maximum a-posteriori probability (MAP) criteria is used to derive the receiver. The decoding is done using a turbo-code decoder with modifications which are discussed. Iterations of the system are used to attain large performance improvements over conventional systems.
Polycrystalline silicon thin film transistors on Corning 7059 glass substrates using short time, low-temperature processing (1993)

A new fabrication process for polycrystalline silicon thin film transistors on 7059 glass substrates is reported. This unique fabrication process has the advantages of short processing time and low processing temperature (≤600 °C). The processing is based on the key step of using an ultrathin Pd layer, introduced to the surface of the glass prior to the deposition of an a-Si:H film, to reduce the crystallization time and temperature. It is also based on using an electron cyclotron resonance hydrogen plasma to reduced the passivation time. The n-channel TFTs produced by this new fabrication process have mobilities of 20 cm2/V s, and off-currents of 0.5 pA/μm.
Beyond the Watson-Crick double helix: design of functional nucleic acids in silico, in tube, and in cell (2003)

The structures and thermodynamic properties of non-Watson-Crick structures in RNA and DNA are described. The recent data on dangling ends in RNA, peptide nucleic acid (PNA), triplex, and G-quadruplex have resulted in an understanding of the catalysis, tertiary contact domains, and biological functions associated with these unpaired regions and special helices, and are useful in developing functional nucleic acids in cell.
Carbon Cycling in Anabaena sp. PCC 7120. Sucrose Synthesis in the Heterocysts and Possible Role in Nitrogen Fixation (2007)

Nitrogen (N) available to plants mostly originates from N(2) fixation carried out by prokaryotes. Certain cyanobacterial species contribute to this energetically expensive process related to carbon (C) metabolism. Several filamentous strains differentiate heterocysts, specialized N(2)-fixing cells. To understand how C and N metabolism are regulated in photodiazotrophically grown organisms, we investigated the role of sucrose (Suc) biosynthesis in N(2) fixation in Anabaena sp. PCC 7120 (also known as Nostoc sp. PCC 7120). The presence of two Suc-phosphate synthases (SPS), SPS-A and SPS-B, directly involved in Suc synthesis with different glucosyl donor specificity, seems to be important in the N(2)-fixing filament. Measurement of enzyme activity and polypeptide levels plus reverse transcription-polymerase chain reaction experiments showed that total SPS expression is greater in cells grown in N(2) versus combined N conditions. Only SPS-B, however, was seen to be active in the heterocyst, as confirmed by analysis of green fluorescent protein reporters. SPS-B gene expression is likely controlled at the transcriptional initiation level, probably in relation to a global N regulator. Metabolic control analysis indicated that the metabolism of glycogen and Suc is likely interconnected in N(2)-fixing filaments. These findings suggest that N(2) fixation may be spatially compatible with Suc synthesis and support the role of the disaccharide as an intermediate in the reduced C flux in heterocyst-forming cyanobacteria.
Genetically encoded calcium indicators for multi-color neural activity imaging and combination with optogenetics (2013)

Genetically encoded calcium indicators (GECIs) are powerful tools for systems neuroscience. Here we describe red, single-wavelength GECIs, "RCaMPs," engineered from circular permutation of the thermostable red fluorescent protein mRuby. High-resolution crystal structures of mRuby, the red sensor RCaMP, and the recently published red GECI R-GECO1 give insight into the chromophore environments of the Ca(2+)-bound state of the sensors and the engineered protein domain interfaces of the different indicators. We characterized the biophysical properties and performance of RCaMP sensors in vitro and in vivo in Caenorhabditis elegans, Drosophila larvae, and larval zebrafish. Further, we demonstrate 2-color calcium imaging both within the same cell (registering mitochondrial and somatic [Ca(2+)]) and between two populations of cells: neurons and astrocytes. Finally, we perform integrated optogenetics experiments, wherein neural activation via channelrhodopsin-2 (ChR2) or a red-shifted variant, and activity imaging via RCaMP or GCaMP, are conducted simultaneously, with the ChR2/RCaMP pair providing independently addressable spectral channels. Using this paradigm, we measure calcium responses of naturalistic and ChR2-evoked muscle contractions in vivo in crawling C. elegans. We systematically compare the RCaMP sensors to R-GECO1, in terms of action potential-evoked fluorescence increases in neurons, photobleaching, and photoswitching. R-GECO1 displays higher Ca(2+) affinity and larger dynamic range than RCaMP, but exhibits significant photoactivation with blue and green light, suggesting that integrated channelrhodopsin-based optogenetics using R-GECO1 may be subject to artifact. Finally, we create and test blue, cyan, and yellow variants engineered from GCaMP by rational design. This engineered set of chromatic variants facilitates new experiments in functional imaging and optogenetics.
A free-space adaptive FMM-Based PDE solver in three dimensions (2011)

We present a kernel-independent, adaptive fast multipole method (FMM) of arbitrary order accuracy for solving elliptic PDEs in three dimensions with radiation and periodic boundary conditions. The algorithm requires only the ability to evaluate the Green's function for the governing equation and a representation of the source distribution (the right-hand side) that can be evaluated at arbitrary points. The performance is accelerated in three ways. First, we construct a piecewise polynomial approximation of the right-hand side and compute far-field expansions in the FMM from the coefficients of this approximation. Second, we precompute tables of quadratures to handle the near-field interactions on adaptive octree data structures, keeping the total storage requirements in check through the exploitation of symmetries. Third, we employ shared-memory parallelization methods and load-balancing techniques to accelerate the major algorithmic loops of the FMM. We present numerical examples for the Laplace, modified Helmholtz and Stokes equations.
Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution (2009)

Recent advances in next generation sequencing have made it possible to precisely characterize all somatic coding mutations that occur during the development and progression of individual cancers. Here we used these approaches to sequence the genomes (>43-fold coverage) and transcriptomes of an oestrogen-receptor-alpha-positive metastatic lobular breast cancer at depth. We found 32 somatic non-synonymous coding mutations present in the metastasis, and measured the frequency of these somatic mutations in DNA from the primary tumour of the same patient, which arose 9 years earlier. Five of the 32 mutations (in ABCB11, HAUS3, SLC24A4, SNX4 and PALB2) were prevalent in the DNA of the primary tumour removed at diagnosis 9 years earlier, six (in KIF1C, USP28, MYH8, MORC1, KIAA1468 and RNASEH2A) were present at lower frequencies (1-13%), 19 were not detected in the primary tumour, and two were undetermined. The combined analysis of genome and transcriptome data revealed two new RNA-editing events that recode the amino acid sequence of SRP9 and COG3. Taken together, our data show that single nucleotide mutational heterogeneity can be a property of low or intermediate grade primary breast cancers and that significant evolution can occur with disease progression.
Multiple Myeloma (1997)

Multiple myeloma is a disorder in which malignant plasma cells accumulate in the bone marrow and produce an immunoglobulin, usually monoclonal IgG or IgA. Common complications of overt multiple myeloma include recurrent bacterial infections, anemia, osteolytic lesions, and renal insufficiency. Multiple myeloma is responsible for about 1 percent of all cancer-related deaths in Western countries. Its epidemiologic pattern remains obscure, and its cause is unknown.1 Monoclonal Gammopathy of Undetermined Significance and the Natural History of Multiple MyelomaA monoclonal gammopathy of undetermined significance is marked by the presence in the serum of monoclonal IgG or IgA without evidence of multiple . . .
CD28/B7 Costimulation: A Review (1998)

The current model of T cell activation requires two signals. The first signal is specific, requiring T cell receptor recognition and binding to MHC/Antigen presented by an antigen-presenting cell. The second signal is nonspecific, resulting from the binding of B7 ligand on the antigen-presenting cell with its receptor, CD28, on the T cell. If both signals are provided, the T cell will proliferate and secrete cytokines. Recently, it has been shown that CTLA4, another receptor for B7 that is upregulated following T cell after activation, can deliver an inhibitory signal, downregulating T cell proliferation. The B7 family of ligands has two family members, B7-1 and B7-2. They both bind to CD28 and CTLA4, but they differ in their binding affinity, structure, and temporal expression. Considerable research has been done on the CD28/B7 costimulatory pathway. Different ways of manipulating this pathway could provide insights into the mechanism and treatment of opposing pathological states. Blocking the CD28/B7 pathway could result in immunosuppression, with implications for the treatment of autoimmune diseases, organ transplantation, and graft vs. host disease. Activating the CD28/B7 pathway could be useful for including the immune system to recognize and eliminate tumors that evade the immune system. Finally, the CD28/B7 pathway could be involved with maintaining immune tolerance, as recent studies suggest the preferential binding of the B7-CTLA4 pathway results in the down-regulation of the responding T cells. Thus, the B7/CD28/CTLA4 pathway has the ability to both positively and negatively regulate immune responses.
Multiple-description coding (MDC) of speech with an invertible auditory model (2003)

Network signal processing aspects dominate in speech and audio coding applications such as Internet telephony or packet radio networks. We demonstrate that our approach to speech coding in a perceptual domain provides an implicit forward error concealment mechanism to handle random erasures of the channel. To this end, the individual acoustic subchannels of our auditory model are grouped into different transport subchannels or packets. Due to the strongly overlapping, redundant filterbank structure of the model, reconstruction of speech without audible degradation becomes possible even if a significant percentage of channels is erased (e.g., up to 40% in a 50-channel auditory model for narrowband speech). We discuss this result both from a hearing-physiology and a frame-theoretic perspective.
Salmonellosis in Disseminated Malignant Diseases (1967)

ALTHOUGH many bacterial infections, such as typhoid fever, diphtheria and pertussis, have been effectively controlled by public-health measures or immunization, the incidence of salmonellosis of man, other than typhoid fever, has been on the increase. This infection usually occurs in otherwise healthy subjects, notably in the form of food poisoning and gastroenteritis; it is seen less commonly as focal infection of various organs and salmonella fever; and finally, salmonellas are present in carriers, with or without antecedent overt illness. In addition, salmonellosis may complicate diseases such as malaria, relapsing fever, sickle-cell anemia, bartonellosis or Carrión's disease and liver disease.1 2 3 Several . . .
FATE and DESTINI: a framework for cloud recovery testing (2011)

As the cloud era begins and failures become commonplace, failure recovery becomes a critical factor in the availability, reliability and performance of cloud services. Unfortunately, recovery problems still take place, causing downtimes, data loss, and many other problems. We propose a new testing framework for cloud recovery: FATE (Failure Testing Service) and DESTINI (Declarative Testing Specifications). With FATE, recovery is systematically tested in the face of multiple failures. With DESTINI, correct recovery is specified clearly, concisely, and precisely. We have integrated our framework to several cloud systems (e.g., HDFS [33]), explored over 40,000 failure scenarios, wrote 74 specifications, found 16 new bugs, and reproduced 51 old bugs.
Effects of 90Y-microspheres on liver tumors: comparison of intratumoral injection method and intra-arterial injection method. (2000)

Both methods (intratumoral treatment and intraarterial treatment) showed a significantly good response rate and prolonged survival time compared with those of the control groups. However, no significant difference was found in the response rate or survival time between intratumoral treatment and intra-arterial treatment.
Systemic sclerosis: an update. (2008)

Systemic sclerosis (SSc) is a complex and heterogeneous chronic illness characterized by substantial patient to patient variability in clinical manifestations, internal organ involvement, and outcome. Genetic factors contribute to disease susceptibility, but environmental influences also play a significant role. The pathogenesis of SSc encompasses vascular, immunological, and fibrotic processes, which contribute to clinical manifestations and morbidity and must be addressed in the treatment plan. Although vascular interventions appear to reduce the frequency and severity of complications, such as scleroderma renal crisis and pulmonary hypertension, current therapies generally target the immune component of SSc in a non-selective fashion and have largely failed as diseases-modifying interventions. Newer insights into the mechanisms underlying autoimmunity, vascular injury and destruction, and particularly tissue fibrosis provide novel potential targets for therapy. Transforming growth factor-ss is a ubiquitous cytokine that appears to contribute to fibroblast activation, collagen overproduction, and pathological tissue fibrosis. Neutralizing antibodies and small molecules that block TGF-beta activation or function are effective in shutting down TGF-beta signaling and selectively inhibit the progression of fibrosis and may be entering clinical trials for the treatment of SSc.
Use of respiratory quotient as a control parameter for optimum oxygen supply and scale‐up of 2,3‐butanediol production under microaerobic conditions (1994)

The respiratory quotient (RQ) was found to be a suitable control parameter for optimum oxygen supply for the production of 2,3-butanediol + acetoin under microaerobic conditions. In laboratory scale continuous cultures optimum production of 2,3-butanediol + acetoin was obtained at an RQ value between 4.0 to 4.5. This agreed well with optimum RQ value (4.0) stoichiometrically derived from the bioreactions involved. In fed-batch cultures product concentrations as high as 102.9 g/L (96.0 g/L butanediol + 6.9 g/L acetoin) can be achieved within 32 h cultivation with an RQ control algorithm for oxygen supply. Under similar conditions only 85.7 g/L product (77.6 g/L butanediol + 8.1 g/L acetoin) was obtained with control of constant oxygen supply rate throughout the cultivation.In pilot scale batch cultures under identical oxygen supply rate the achievable RQ value was found to be strongly influenced by the reactor type and scale. The initial oxygen supply rate influenced the achievable RQ as well. However, in all the reactors studied the specific product formation rate of cells in the exponential growth phase was only a function of RQ. The same optimum RQ value as found in continuous cultures was obtained. It was thus concluded that RQ can be used as a control parameter for optimum production of 2,3-butanediol + acetoin in both laboratory and pilot plant scale reactors.