Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular Heterogeneity and Receptor Coamplification Drive Resistance to Targeted Therapy in MET-Amplified Esophagogastric Cancer.

UNLABELLED MET inhibition is effective in some patients with MET-amplified esophagogastric cancer (EGC), but understanding acquired and de novo resistance mechanisms will be critical to improving therapy. We identified KRAS mutation as a novel cause of acquired resistance in a patient after a 2-year response to a MET inhibitor. We also observed that 40% to 50% of patients with MET-amplified EGC harbor coamplification of HER2 and/or EGFR concurrently in the same tumor cells, which can drive de novo resistance. One patient with concurrent MET and HER2 amplification was refractory to HER2 blockade, but responded to combined MET/HER2 inhibition. We also found striking heterogeneity in MET amplification between distinct metastatic lesions and primary tumors in individual patients with EGC. In these patients, MET inhibition led to mixed responses and disease progression through outgrowth of non-MET-amplified clones, which could be monitored in circulating tumor DNA. Thus, receptor coamplification and molecular heterogeneity may be key drivers of clinical resistance in MET-amplified EGC. SIGNIFICANCE Coamplification of driver oncogenes occurs frequently in EGC and can drive therapeutic resistance, supporting a role for comprehensive molecular analysis prior to targeted therapy. EGCs can also exhibit extensive heterogeneity in gene amplification between distinct tumor lesions within the same patient, suggesting that molecular profiling of a single-lesion biopsy may be insufficient to guide targeted therapy selection.
Effects of Bone Vibrator Position on Auditory Spatial Perception Tasks

Objective: This study assessed listeners’ ability to localize spatially differentiated virtual audio signals delivered by bone conduction (BC) vibrators and circumaural air conduction (AC) headphones. Background: Although the skull offers little intracranial sound wave attenuation, previous studies have demonstrated listeners’ ability to localize auditory signals delivered by a pair of BC vibrators coupled to the mandibular condyle bones. The current study extended this research to other BC vibrator locations on the skull. Method: Each participant listened to virtual audio signals originating from 16 different horizontal locations using circumaural headphones or BC vibrators placed in front of, above, or behind the listener’s ears. The listener’s task was to indicate the signal’s perceived direction of origin. Results: Localization accuracy with the BC front and BC top positions was comparable to that with the headphones, but responses for the BC back position were less accurate than both the headphones and BC front position. Conclusion: This study supports the conclusion of previous studies that listeners can localize virtual 3D signals equally well using AC and BC transducers. Based on these results, it is apparent that BC devices could be substituted for AC headphones with little to no localization performance degradation. Application: BC headphones can be used when spatial auditory information needs to be delivered without occluding the ears. Although vibrator placement in front of the ears appears optimal from the localization standpoint, the top or back position may be acceptable from an operational standpoint or if the BC system is integrated into headgear.
Metabolic Engineering of Acetaldehyde Production by Streptococcus thermophilus

ABSTRACT The process of acetaldehyde formation by the yogurt bacterium Streptococcus thermophilus is described in this paper. Attention was focused on one specific reaction for acetaldehyde formation catalyzed by serine hydroxymethyltransferase (SHMT), encoded by the glyA gene. In S. thermophilus, SHMT also possesses threonine aldolase (TA) activity, the interconversion of threonine into glycine and acetaldehyde. In this work, several wild-type S. thermophilus strains were screened for acetaldehyde production in the presence and absence of l-threonine. Supplementation of the growth medium with l-threonine led to an increase in acetaldehyde production. Furthermore, acetaldehyde formation during fermentation could be correlated to the TA activity of SHMT. To study the physiological role of SHMT, a glyA mutant was constructed by gene disruption. Inactivation of glyA resulted in a severe reduction in TA activity and complete loss of acetaldehyde formation during fermentation. Subsequently, an S. thermophilus strain was constructed in which the glyA gene was cloned under the control of a strong promoter (PLacA). When this strain was used for fermentation, an increase in TA activity and in acetaldehyde and folic acid production was observed. These results show that, in S. thermophilus, SHMT, displaying TA activity, constitutes the main pathway for acetaldehyde formation under our experimental conditions. These findings can be used to control and improve acetaldehyde production in fermented (dairy) products with S. thermophilus as starter culture.
Constructing Well-Organized Wireless Sensor Networks with Low-level Identification

: In most distributed systems, naming of nodes for low-level communication leverages topological location (such as node addresses) and is independent of any application. In this paper, we investigate an emerging class of distributed systems where low-level communication does not rely on network topological location. Rather, low-level communication is based on attributes that are external to the network topology and relevant to the application. When combined with dense deployment of nodes, this kind of named data enables in-network processing for data aggregation, collaborative signal processing and similar problems. These approaches are essential for emerging applications such as sensor networks where resources such as bandwidth and energy are limited. This paper is the first description of the software architecture that supports named data and in-network processing in an operational, multi-application sensor-network. We show that approaches such as in-network aggregation and nested queries can significantly affect network traffic. In one experiment aggregation reduces traffic by up to 42% and nested queries reduce loss rates by 30%. Although aggregation has been previously studied in simulation, this paper demonstrates nested queries as another form of in-network processing and it presents the first evaluation of these approaches over an operational testbed.
Host defenses in herpes simplex infections of the nervous system: effect of antibody on disease and viral spread

BALB/c mice passively immunized with antibody to herpes simplex virus type 1 and challenged in the footpad with 10(5.7) plaque-forming units of herpes simplex virus type 1 were shown to be protected from neurological disease and death compared with control mice treated with normal serum or antibody to Sindbis virus. One hundred percent of untreated mice had virus recoverable from dorsal root ganglia by 48 h after infection. Whereas amputation of the infected limb at 48 h had no effect, antibody administration (resulting in titers of 1:8 and 1:16) was found to prevent acute neurological disease if administered no later than 48 h after infection. Antibody also restricted the extent of latent infection in the lumbosacral ganglia. The data provide strong evidence that antibody is effective in preventing spread of virus both in the peripheral nervous system and in central nervous system (spinal cord) tissue.
Velocity Correlations of a Brownian Particle Velocity Correlations of a Brownian Particle

A new derivation of the velocity correlations of a thermally fluctuating Brownian particle is shown by direct calculation from a stochastic hydrodynamic model in which the fluid-particle coupling is treated in a simple manner. The model significantly simplifies the calculation of statistics of a particle and has the virtue of being readily amenable to numerical simulation. To show that the model correctly captures physical features of a Brownian particle the diffusion coefficient in three dimensions is computed and shown to have the correct scaling in the physical parameters. The velocity correlation function for both short and long times scales is then discussed. It is found for short times that the velocity correlation of a particle satisfies an equipartition principle. For long times the autocorrelation function is shown to have non-exponential decay of algebraic order τ capturing well-known hydrodynamic effects [1]. The results are then compared with numerical simulations of the hydrodynamic model using the computational method proposed in [2].
The Tumor Suppressor Kruppel-Like Factor 6 Is a Novel Aryl Hydrocarbon Receptor DNA Binding Partner

The aryl hydrocarbon receptor (AhR) is a ligand-mediated basic helix-loop-helix transcription factor of the Per/Arnt/Sim family that regulates adaptive and toxic responses to a variety of chemical pollutants, including polycyclic aromatic hydrocarbons and halogenated aromatic hydrocarbons, most notably 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Ligand activation leads to AhR nuclear translocation and binding to a xenobiotic response element (XRE) in association with the Arnt to regulate gene expression. Several recent genome-wide transcriptional studies identified numerous AhR target genes that lack the canonical XRE recognition site in the promoter regions. Characterization of one such target gene, the plasminogen activator inhibitor 1, identified a novel nonconsensus XRE (NC-XRE) that confers TCDD responsiveness independently of the Arnt protein. Studies reported here show that the NC-XRE is a recognition site for the AhR and a new binding partner, the Kruppel-like factor (KLF) family member KLF6. In vivo chromatin immunoprecipitations and in vitro DNA binding studies demonstrate that the AhR and KLF6 proteins form an obligatory heterodimer necessary for NC-XRE binding. Mutational analyses show that the protein-protein interactions involve the AhR C terminus and KLF6 N terminus, respectively. Moreover, NC-XRE binding depends on the 5′ basic region in KLF6 rather than the previously characterized zinc finger DNA binding domain. Collectively, the results unmask a novel AhR signaling mechanism distinct from the canonical XRE-driven process that will enrich our future understanding of AhR biology.
12118 - Produção de biomassa e CO 2 equivalente em sistema agrossilvipastoril: uma aplicação da dinâmica de sistema Estimated of biomass and CO 2 equivalent by an agrosilvopastoral system: through the system dynamics

Resumo: Os Sistemas Agroflorestais (SAFs) mostram-se como uma alternativa social e economica as consequencias da acao antropica sobre o meio ambiente. B uscou-se verificar a dinâmica da producao de biomassa e o estoque de CO 2 equivalente no SAF, em area de caatinga no estado do Ceara. A area de estudo compreendeu o SAF localizado na Fazenda Crioula, pertencente ao Centro Nacional de Pesquisa de Caprinos da Embrapa, estando situada no municipio de Sobral – CE. Utilizou-se como ferramenta de elaboracao do modelo o software Vensim®. As simulacoes basearam-se na determinacao de cenarios para uso da terra (culturas agricolas) e manejo da caatinga. Os resultados demonstraram que o sistema foi capaz agregar renda por meio da venda dos produtos agricolas e a comercializacao do CO 2 equivalente caso existisse um mercado especifico para o produtor. O modelo desenvolvido para SAF oriundo desta pesquisa mostrou-se capaz de contribuir com as pesquisas ja desenvolvidas atualmente, bem como para a sustentabilidade e viabilidade desse modelo de producao, por meio da diversificacao de atividades e produtos, favorecendo uma geracao de renda mais harmonica no tempo. Palavras -Chave: Caatinga, Modelagem, Servicos ambientais.
Characterization of a monoclonal anti‐porcine CD3 antibody

Huang CA, Lorf T, Arn JS, Koo GC, Blake T, Sachs DH. Characterization of a monoclonal anti‐porcine CD3 antibody. Xenotransplantation 1999; 6: 201‐212. © Munksgaard, Copenhagen
Replication of type 1 human immunodeficiency viruses containing linker substitution mutations in the -201 to -130 region of the long terminal repeat

In previous transfection analyses using the chloramphenicol acetyltransferase reporter gene system, we determined that linker substitution (LS) mutations between -201 and -130 (relative to the transcription start site) of the human immunodeficiency virus type 1 long terminal repeat (LTR) caused moderate decreases in LTR transcriptional activity in a T-cell line (S. L. Zeichner, J. Y. H. Kim, and J. C. Alwine, J. Virol. 65:2436-2444, 1991). In order to confirm the significance of this region in the context of viral replication, we constructed several of these LS mutations (-201 to -184, -183 to -166, -165 to -148, and -148 to -130) in proviruses and prepared viral stocks by cocultivation of transfected RD cells with CEMx174 cells. In addition, two mutations between -93 and -76 and between -75 and -58 were utilized, since they affect the nuclear factor kappa B (NF-kappa B)- and Sp1-binding sites and were expected to diminish viral replication. Our results suggest that while transfection analyses offer an adequate approximation of the effects of the LS mutations, the analysis of viral replication using a mutant viral stock presents a more accurate picture, which is sometimes at variance with the transfection results. Three mutants (-201/-184 NXS, -165/-148 NXS, and -147/-130 NXS) had effects on viral replication that were much more severe than the effects predicted from their performance in transfection analyses, and the effects of two LS mutations (-201/-184 NXS and -183/-166 NXS) were not predicted by their effects in transfection. In addition, we observed cell type-specific permissiveness to replication of some mutant viruses. In the cell types tested, the LS mutations indicated an apparent requirement not only for the intact NF-kappa B and SP1-binding sites but also for several regions between -201 and -130 not previously associated with viral infectivity.
Transcriptome Profiling of Trypanosoma brucei Development in the Tsetse Fly Vector Glossina morsitans

African trypanosomes, the causative agents of sleeping sickness in humans and nagana in animals, have a complex digenetic life cycle between a mammalian host and an insect vector, the blood-feeding tsetse fly. Although the importance of the insect vector to transmit the disease was first realized over a century ago, many aspects of trypanosome development in tsetse have not progressed beyond a morphological analysis, mainly due to considerable challenges to obtain sufficient material for molecular studies. Here, we used high-throughput RNA-Sequencing (RNA-Seq) to profile Trypanosoma brucei transcript levels in three distinct tissues of the tsetse fly, namely the midgut, proventriculus and salivary glands. Consistent with current knowledge and providing a proof of principle, transcripts coding for procyclin isoforms and several components of the cytochrome oxidase complex were highly up-regulated in the midgut transcriptome, whereas transcripts encoding metacyclic VSGs (mVSGs) and the surface coat protein brucei alanine rich protein or BARP were extremely up-regulated in the salivary gland transcriptome. Gene ontology analysis also supported the up-regulation of biological processes such as DNA metabolism and DNA replication in the proventriculus transcriptome and major changes in signal transduction and cyclic nucleotide metabolism in the salivary gland transcriptome. Our data highlight a small repertoire of expressed mVSGs and potential signaling pathways involving receptor-type adenylate cyclases and members of a surface carboxylate transporter family, called PADs (Proteins Associated with Differentiation), to cope with the changing environment, as well as RNA-binding proteins as a possible global regulators of gene expression.
Small airways function and molecular markers in exhaled air in mild asthma

Background: Several studies suggest that the periphery of the lung is the major site of inflammation in asthma. Fractional exhaled nitric oxide (Feno) and 8-isoprostane have been proposed as biomarkers of inflammation and oxidative stress. We therefore hypothesised that small airway dysfunction in asthma is of inflammatory origin that can be detected by molecular markers in exhaled air. To test this hypothesis, we examined the relationship of Feno and 8-isoprostane in exhaled air with small airways function as assessed by the single breath nitrogen test. Methods: Sixteen patients (14 women) with mild atopic asthma (forced expiratory volume in 1 second >80% predicted) of mean (SD) age 23.0 (5.5) years participated in a cross sectional study. Feno was recorded by chemiluminescence and 8-isoprostane was measured by ELISA in concentrated exhaled breath condensate. The slope of phase III (δN2) and the closing volume (CV) were assessed from the single breath washout curve. Results: The median Feno level was 30.4 ppb (range 10.1–82.8), the median 8-isoprostane concentration in exhaled breath condensate was 2.2 pg/ml (range 1.6–2.7), and the mean (SD) δN2 value was 1.1 (0.4)% N2/l. Feno was positively associated with δN2 (rs = 0.54, p = 0.032) while 8-isoprostane was inversely correlated with FEV1% predicted (rs = −0.58; p = 0.017) and CV as a percentage of vital capacity (rs = 0.58; p = 0.019). Conclusions: Feno and 8-isoprostane in exhaled air are associated with small airways function in mild asthma. This suggests that these markers reflect small airway inflammation and favours a role for them as disease markers that is complementary to spirometry in the monitoring of patients with asthma.
Aicardi's Epilepsy in Children.

Part I. General Aspects 1. Epilepsy: Overview and Definitions 2. Classification of Epileptic Seizures and Epilepsies Part II. Major Types of Epileptic Seizures in Childhood and Corresponding Epileptic Syndromes 3. Infantile Spasms and Related Syndromes 4. LennoxuGastaut Syndrome 5. Severe Myoclonic Epilepsy: Dravet Syndrome 6. Epilepsy Characterized by Myoclonic Seizures 7. Progressive Myoclonic Epilepsies 8. Epilepsies with Typical Absence Seizures 9. Epilepsies with Generalized Tonic-Closure Seizures 10. Epilepsies Characterized by Partial Seizures 11. Rasmussen Syndrome 12. Landau-Kleffner Syndrome and Continuous Spike-Wave during Slow Sleep Part III. Epileptic Manifestations in Relation to Age, Cause, Duration, and Precipitation of Seizures 13. Neonatal Seizures 14. Epilepsy in Infants 15. Febrile Convulsions 16. Occasional Seizures Other Than Febrile Convulsions 17. Status Epilepticus 18. Stimulus-Sensitive Epilepsies 19. Post-Traumatic Epilepsy 20. Epilepsies as a Presenting Manifestation of Brain Tumors and of Other Selected Brain Disorders Part IV. Selected Aspects of the Diagnosis, Prognosis, and Treatment of Convulsive Disorders in Children 21. Diagnosis and Differential Diagnosis 22. General Aspects of Prognosis 23. Genetics 24. General Principles of Management 25. Medical Treatment 26. Surgical Treatmen
Multi-core Deployment Optimization Using Simulated Annealing and Ant Colony Optimization

This work introduces a hybrid metaheuristic algorithm for solving the problem of multi-core deployment optimization (MCDO). It extends prior work using Ant Colony Optimization to solve MCDO by initially seeding the pheromone matrix with the output of a Simulated Annealing metaheuristic. This work also removes a number of critical simplifying assumptions from the MCDO model. Across 28, 800 different algorithm inputs, the hybridized algorithm is shown to have a median improvement in makespan time of 7.2% versus the nonhybrid version, as well as a median reduction of 74% in execution time. On a dataset of 50 MCDO problems with known optimal solutions, the median hybrid algorithm solution is 16.5% worse than known optimal.
Factors affecting ERP system effectiveness in post-implementation stage within Malaysian manufacturing companies

Enterprise resource planning ERP system has become one of the main pre-requisites for many companies enabling them to compete in the local and global market, a price of entry to gain a competitive advantage in the global economy, and a backbone for e-business as well as for the whole supply chain. Many companies are still reluctant to implement ERP system and therefore they will not be able to join the supply chain of several global and local companies where ERP system has become a pre-requisite and a price of entry for the global economy. This study has investigated the impact of ERP system on supply chain performance with respect to top management support, employee involvement, and cultural fit in the context of Malaysian manufacturing companies that are using ERP system and this is to fill up the gap in post-implementation stage. The study found that employee involvement, top management support, and cultural fit partially affects positively and significantly the relationship between ERP system and supply chain performance.
Intrauterine death of one twin, with rescue of the other, in twin–twin transfusion syndrome

Single intrauterine death may occur in twin–twin transfusion syndrome. We investigated why the outcome of the surviving twin is fairly good when the donor twin dies first compared with when the recipient twin dies first. A detailed hemodynamic study was performed using Doppler ultrasound in a twin pregnancy affected by twin–twin transfusion syndrome before and after a single intrauterine death that occurred in the donor twin at 26 weeks' gestation. The recipient twin was expected to die due to severe right cardiac failure with functional stenosis of the pulmonary artery 2 days before the cotwin's death. The donor twin's death caused a prompt resolution of cardiac failure and improvement in other indices, including flow velocity waveform patterns of the umbilical vein, the middle cerebral artery and the ductus venosus. A healthy, premature female neonate weighing 1630 g with a hemoglobin concentration of 17.8 g/dL was delivered by Cesarean section following rupture of the fetal membranes 28 days after the episode. Hemorrhaging from the surviving twin to the dead twin that occurred just before or after the cotwin's death may have contributed to the decrease in volume overload in the recipient twin, leading to a prompt amelioration of the critical hemodynamic indices. The early death of the donor twin may thus have played a significant role in improving the status of the recipient twin in this case of twin–twin transfusion syndrome. Copyright © 2002 ISUOG
Apoptosis leads to a degradation of vital components of active nuclear transport and a dissociation of the nuclear lamina

Apoptosis, a physiologically critical process, is characterized by a destruction of the cell after sequential degradation of key cellular components. Here, we set out to explore the fate of the physiologically indispensable nuclear envelope (NE) in this process. The NE mediates the critical nucleocytoplasmic transport through nuclear pore complexes (NPCs). In addition, the NE is involved in gene expression and contributes significantly to the overall structure and mechanical stability of the cell nucleus through the nuclear lamina, which underlies the entire nucleoplasmic face of the NE and thereby interconnects the NPCs, the NE, and the genomic material. Using the nano-imaging and mechanical probing approach atomic force microscopy (AFM) and biochemical methods, we unveiled the fate of the NE during apoptosis. The doomed NE sustains a degradation of both the mediators of the critical selective nucleocytoplasmic transport, namely NPC cytoplasmic filaments and basket, and the nuclear lamina. These observations are paralleled by marked softening and destabilization of the NE and the detection of vesicle-like nuclear fragments. We conclude that destruction of the cell nucleus during apoptosis proceeds in a strategic fashion. Degradation of NPC cytoplasmic filaments and basket shuts down the critical selective nucleocytoplasmic cross-talk. Degradation of the nuclear lamina disrupts the pivotal connection between the NE and the chromatin, breaks up the overall nuclear architecture, and softens the NE, thereby enabling the formation of nuclear fragments at later stages of apoptosis.