scholarly journals Sensor-Integrated Microfluidic Approaches for Liquid Biopsies Applications in Early Detection of Cancer

Sensors ◽  
2020 ◽  
Vol 20 (5) ◽  
pp. 1317 ◽  
Author(s):  
Jessica Sierra ◽  
José Marrugo-Ramírez ◽  
Romen Rodriguez-Trujillo ◽  
Mònica Mir ◽  
Josep Samitier
Keyword(s):  
Lower Risk ◽  
Causes Of Death ◽  
Histological Analysis ◽  
Early Stage ◽  
Low Cost ◽  
Liquid Biopsies ◽  
Fully Integrated ◽  
Minimal Invasiveness ◽  
Molecular Information ◽  
Detection Technologies

Cancer represents one of the conditions with the most causes of death worldwide. Common methods for its diagnosis are based on tissue biopsies—the extraction of tissue from the primary tumor, which is used for its histological analysis. However, this technique represents a risk for the patient, along with being expensive and time-consuming and so it cannot be frequently used to follow the progress of the disease. Liquid biopsy is a new cancer diagnostic alternative, which allows the analysis of the molecular information of the solid tumors via a body fluid draw. This fluid-based diagnostic method displays relevant advantages, including its minimal invasiveness, lower risk, use as often as required, it can be analyzed with the use of microfluidic-based platforms with low consumption of reagent, and it does not require specialized personnel and expensive equipment for the diagnosis. In recent years, the integration of sensors in microfluidics lab-on-a-chip devices was performed for liquid biopsies applications, granting significant advantages in the separation and detection of circulating tumor nucleic acids (ctNAs), circulating tumor cells (CTCs) and exosomes. The improvements in isolation and detection technologies offer increasingly sensitive and selective equipment’s, and the integration in microfluidic devices provides a better characterization and analysis of these biomarkers. These fully integrated systems will facilitate the generation of fully automatized platforms at low-cost for compact cancer diagnosis systems at an early stage and for the prediction and prognosis of cancer treatment through the biomarkers for personalized tumor analysis.

Case Study and Lessons Learnt for the 1St Fully Integrated Hwu Well Abandonment at Field a Offshore Malaysia

2021 ◽  
Author(s):  
Shahril Yang Shahril Shahril ◽  
Tengku Khairul Izwan Tengku Ahmad Tengku Khairul Tengku Khairul ◽  
Khalieff Fathiee Lokman Zakey Khalieff Fathiee Khalieff
Keyword(s):  
Early Stage ◽  
Low Cost ◽  
Project Planning ◽  
Lessons Learned ◽  
Point Of View ◽  
Fully Integrated ◽  
Practical Experiences ◽  
Well Abandonment ◽  
Technical Operation ◽  
Drilling Rigs

Abstract Uzma was awarded with 1st integrated well abandonment under Provision of Well Abandonment Integrated Services (WAISE) in 2018. Total of 22 wells were plug & abandonment with average 10 to 20 days per well were spent to complete the work. The scope of works is inclusive providing Project Management Team, Hydraulic Workover Unit, Accommodation Work Boat, Supply Vessels, and P&A services. This paper will highlight the practical experiences and capture the lessons learned obtained executing 1st integrated well abandonment campaign in Field A Offshore Malaysia. This paper presents the overall project lesson learnt for 1st integrated well abandonment embarked from early stage of project planning, preparation, acceptance, technical, operation & project close out. The lesson learnt will be beneficial for all Operator & Contractor Company involving with integrated well abandonment. This paper also presents capability of hydraulic workover unit and recommendation for future of low-cost well's plug and abandonment. Plug and abandonment operations with conventional hydraulic workover units have an enormous impact on low-cost plug and abandonment campaign in Malaysia compared with conventional drilling rigs. In essence, the lessons learned and insights gained throughout abandonment campaigns will keep accumulating with time to feed into the knowledge and experience vault. With proper project lesson learnt, many success cases and best practices can be emulated both from technical and commercial point of view. This lesson learnt will be beneficial for all Operator & Contractor Company involving with integrated well abandonment.

scholarly journals Automation of absolute protein-ligand binding free energy calculations for docking refinement and compound evaluation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Germano Heinzelmann ◽  
Michael K. Gilson
Keyword(s):  
Free Energy ◽  
Early Stage ◽  
Binding Free Energy ◽  
Low Cost ◽  
Free Energy Calculations ◽  
Free Energies ◽  
Energy Calculations ◽  
Drug Candidates ◽  
Binding Free Energy Calculations ◽  
Binding Free Energies

AbstractAbsolute binding free energy calculations with explicit solvent molecular simulations can provide estimates of protein-ligand affinities, and thus reduce the time and costs needed to find new drug candidates. However, these calculations can be complex to implement and perform. Here, we introduce the software BAT.py, a Python tool that invokes the AMBER simulation package to automate the calculation of binding free energies for a protein with a series of ligands. The software supports the attach-pull-release (APR) and double decoupling (DD) binding free energy methods, as well as the simultaneous decoupling-recoupling (SDR) method, a variant of double decoupling that avoids numerical artifacts associated with charged ligands. We report encouraging initial test applications of this software both to re-rank docked poses and to estimate overall binding free energies. We also show that it is practical to carry out these calculations cheaply by using graphical processing units in common machines that can be built for this purpose. The combination of automation and low cost positions this procedure to be applied in a relatively high-throughput mode and thus stands to enable new applications in early-stage drug discovery.

scholarly journals In-Plane Monolithic Integration of Scaled III-V Photonic Devices

2021 ◽  
Vol 11 (4) ◽  
pp. 1887
Author(s):  
Markus Scherrer ◽  
Noelia Vico Triviño ◽  
Svenja Mauthe ◽  
Preksha Tiwari ◽  
Heinz Schmid ◽  
...  
Keyword(s):  
Integrated Circuits ◽  
High Speed ◽  
Low Cost ◽  
Photonic Devices ◽  
Monolithic Integration ◽  
Light Emitters ◽  
Fully Integrated ◽  
Large Lattice ◽  
Hybrid Iii ◽  
Gain Material

It is a long-standing goal to leverage silicon photonics through the combination of a low-cost advanced silicon platform with III-V-based active gain material. The monolithic integration of the III-V material is ultimately desirable for scalable integrated circuits but inherently challenging due to the large lattice and thermal mismatch with Si. Here, we briefly review different approaches to monolithic III-V integration while focusing on discussing the results achieved using an integration technique called template-assisted selective epitaxy (TASE), which provides some unique opportunities compared to existing state-of-the-art approaches. This method relies on the selective replacement of a prepatterned silicon structure with III-V material and thereby achieves the self-aligned in-plane monolithic integration of III-Vs on silicon. In our group, we have realized several embodiments of TASE for different applications; here, we will focus specifically on in-plane integrated photonic structures due to the ease with which these can be coupled to SOI waveguides and the inherent in-plane doping orientation, which is beneficial to waveguide-coupled architectures. In particular, we will discuss light emitters based on hybrid III-V/Si photonic crystal structures and high-speed InGaAs detectors, both covering the entire telecom wavelength spectral range. This opens a new path towards the realization of fully integrated, densely packed, and scalable photonic integrated circuits.

The biomechanical effects of S-type dynamic cage using Ti and PEEK for ACDF surgery on cervical spine varying loads

2021 ◽  
pp. 039139882110395
Author(s):  
Pechimuthu Susai Manickam ◽  
Sandipan Roy
Keyword(s):  
Disc Degeneration ◽  
Lower Risk ◽  
Mechanical Stability ◽  
Early Stage ◽  
Cervical Disc ◽  
Adjacent Segment ◽  
Stress Profile ◽  
Fe Model ◽  
Cage Subsidence ◽  
Adjacent Disc

Anterior cervical discectomy with fusion (ACDF) is the common method to treat the cervical disc degeneration. The most serious problems in the fusion cages are adjacent disc degeneration, loss of lordosis, pain, subsidence, and migration of the cage. The objective of our work is to develop the three-dimensional finite element (FE) model from C3-C6 and virtually implant a designed S-type dynamic cage at C4-C5 segment of the model. The dynamic cage design will provide mobility in the early stage after ACDF surgery. Titanium (Ti) and PEEK (polyether ether ketone) were used as the material property for the cages. We applied the physiological motions at different loads from 0.5, 1, 1.5, 2.0 Nm to evaluate the dynamic cage design and the biomechanical performances of the designed S-type dynamic cage. It was observed that in all the loading condition the range of motion in the adjacent level was maintained and the maximum stress at the adjacent disc was reduced. The clinical significance of the S-type dynamic cage is better stress profile at the fusion level and adjacent segments which translates into higher rate of fusion, lower risk of cage subsidence, lower risk of adjacent segment degeneration, and good mechanical stability.

Residual ctDNA after treatment predicts early relapse in patients with early-stage NSCLC.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 8517-8517
Author(s):  
Davina Gale ◽  
Katrin Heider ◽  
Malcolm Perry ◽  
Giovanni Marsico ◽  
Andrea Ruiz-Valdepeñas ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Deep Sequencing ◽  
Early Stage ◽  
Post Treatment ◽  
Disease Stage ◽  
Analytical Sensitivity ◽  
Disease Relapse ◽  
Clinical Progression ◽  
Liquid Biopsies ◽  
Early Stage Disease

8517 Background: Liquid biopsies based on circulating tumor DNA (ctDNA) analysis are being investigated for detection of residual disease and recurrence. Conclusive evidence for utility of ctDNA in early-stage non-small cell lung cancer (NSCLC) is awaited. Due to low ctDNA levels in early-stage disease or post-treatment, effective methods require high analytical sensitivity to detect mutant allele fractions (MAF) below 0.01%. Methods: We analysed 363 plasma samples from 88 patients with NSCLC recruited to the LUng cancer CIrculating tumour DNA (LUCID) study, with disease stage I (49%), II (28%) and III (23%). 62% were adenocarcinomas. Plasma was collected before and after treatment, and at 3, 6 and 9 months after surgery (N = 69) or chemoradiotherapy (N = 19). Additional plasma was collected at disease relapse for 17 patients. Median follow-up was 3 years, and 40 patients progressed or died of any cause. We employed the RaDaR™ assay, a highly sensitive personalized assay using deep sequencing of up to 48 tumor-specific variants. Variants identified by tumor exome analysis were tested by deep sequencing of tumor tissue and buffy coat DNA to verify somatic mutations and exclude clonal hematopoiesis. The RaDaR assay demonstrated 90% sensitivity at 0.001% MAF in analytical validation studies. Results: ctDNA was detected in 26% of samples, at median MAF of 0.047% (range: 0.0007% to > 2%), and prior to treatment in 87%, 77% and 24% for disease stage III, II and I respectively. For 62 patients, plasma was collected at a landmark timepoint, between 2 weeks and 4 months after initial treatment. ctDNA detection at the landmark timepoint was strongly predictive of clinical disease relapse, with Hazard Ratio of 20.7 (CI: 7.7-55.5, p-value < 0.0001). All 11 cases with ctDNA detected at landmark had disease progression, a median of 121 days after detection, and these included all 8 patients that relapsed within 300 days of treatment. Across 27 patients whose disease progressed during the study, ctDNA was detected at any timepoint post-treatment in 17 cases, with a median lead time of 203 days, and up to 741 days prior to clinical progression. ctDNA was detected post-treatment, in 13 of the 15 patients that progressed and had ctDNA detected prior to treatment. Conclusions: Our results support an emerging paradigm shift, by demonstrating that liquid biopsies can reliably detect recurrence of NSCLC at a preclinical stage, many months before clinical progression, thereby offering the opportunity for earlier therapeutic intervention. Clinical trial information: NCT04153526.

Development of extracellular vesicles-based classifier for detection of early-stage bladder, ovarian, and pancreatic cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3048-3048
Author(s):  
Juan Pablo Hinestrosa ◽  
Razelle Kurzrock ◽  
Jean Lewis ◽  
Nick Schork ◽  
Ashish M. Kamat ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Confidence Interval ◽  
Extracellular Vesicles ◽  
Metastatic Disease ◽  
Cancer Detection ◽  
Early Stage ◽  
Expression Patterns ◽  
Stepwise Logistic Regression ◽  
Liquid Biopsies ◽  
Cancer Early Detection

3048 Background: Many cancers are lethal because they present with metastatic disease. Because localized/resectable tumors produce vague symptoms, diagnosis is delayed. In pancreatic cancer, only ̃10% of patients survive five years, and it will soon become the second leading cause of cancer-related deaths in the USA. For patients with metastatic disease, the 2- and 5-year survival is < 10% and ̃3%, respectively. For the few patients with local disease, 5-year survival is ̃40%. Many other cancers have comparable differences between early- and late-stage disease. It is apparent a diagnostic assay for early-stage cancers would transform the field by minimizing the need for aggressive surgeries and other harsh interventions, and by its potential to increase survival. Identifying cancer-specific aberrations in blood-based “liquid” biopsies offers a prospect for a non-invasive cancer detection tool. In the bloodstream, there are extracellular vesicles (EVs) with cargoes including membrane and cytosolic proteins, as well as RNA and lipids derived from their parent cells. Methods: We used an alternating current electrokinetics (ACE) microarray to isolate EVs from the plasma of stage I and II bladder (N = 48), ovarian (N = 42), and pancreatic cancer patients (N = 44), and healthy volunteers (N = 110). EVs were analyzed using multiplex protein immunoassays for 54 cancer-related proteins. EV protein expression patterns were analyzed using stepwise logistic regression followed by a split between training and test sets (67%/33% respectively). This process enabled biomarker selection and generation of a classifier to discriminate between cancer and healthy donors. Results: The EV protein-based classifier had an overall area under curve (AUC) of 0.95 with a sensitivity of 71.2% (69.4% – 73.0%, at 95% confidence interval) at > 99% specificity. The classifier’s performance for the pancreatic cancer cohort was very strong, with overall sensitivity of 95.7% (94.6% – 96.9%, at 95% confidence interval) at > 99% specificity. Conclusions: EV-associated proteins may enable early cancer detection where surgical resection is most likely to improve outcomes. The classifier’s performance for the initial three cancers studied showed encouraging results. Future efforts will include examining additional cancer types and evaluating the classifier performance using samples from donors with related benign conditions with the aim of a pan-cancer early detection assay.

The Development of an Electronically Controlled Petrol Injection System

1970 ◽  
Vol 185 (1) ◽  
pp. 95-107
Author(s):  
B. H. Croft
Keyword(s):  
Early Stage ◽  
Low Cost ◽  
High Standard ◽  
Original System ◽  
Injection System ◽  
Specific Power ◽  
Exhaust Emission ◽  
Development Effort ◽  
Electronic Control ◽  
Wide Range

The requirements of the modern automotive petrol engine in relation to higher specific power outputs while retaining good driveability and satisfying the impending exhaust emission control regulations, motivated an investigation into the potential of petrol injection. Consideration of the control requirements and accuracy necessary led, at an early stage, to the selection of electronic control on the basis of control capability, long term reliability, relatively low cost and the potential for future development. The fuel system was designed round the electronic control, manifold injection being used instead of direct injection on the basis of simplicity, lower cost and greater installation flexibility. The original system concept has changed only in detail, development effort being applied to the refinement of the system components to achieve a high standard of performance and the facility to apply the system with minimal modification to a wide range of engine types. The system is described in some detail and typical examples of the system performance on vehicles are presented.

scholarly journals Detection & Classification of Cardiac Arrhythmia

2017 ◽  
Vol 6 (1) ◽  
pp. 31
Author(s):  
Chetan M. Jadhav ◽  
V. K. Bairagi
Keyword(s):  
Cardiac Arrhythmia ◽  
Early Stage ◽  
Low Cost ◽  
Simple Method ◽  
Arrhythmia Detection ◽  
Ecg Signals ◽  
Electrocardiogram Signals ◽  
Electrical Impulses ◽  
Very High

<p>The term Arrhythmia refers to any change from the normal sequence in the electrical impulses. It is also treated as abnormal heart rhythms or irregular heartbeats. The rate of growth of Cardiac Arrhythmia disease is very high &amp; its effects can be observed in any age group in society. Arrhythmia detection can be done in many ways but effective &amp; simple method for detection &amp; diagnosis of  Cardiac Arrhythmia is by doing analysis of Electrocardiogram signals from ECG sensors. ECG signal can give us the detail information of heart activities, so we can use ECG signals to detect the rhythm &amp; behaviour of heart beats resulting into detection &amp; diagnosis of Cardiac Arrhythmia. In this paper new &amp; improved methodology for early Detection &amp; Classification of Cardiac Arrhythmia has been proposed. In this paper ECG signals are captured using ECG sensors &amp; this ECG signals are used &amp; processed to get the required data regarding heart beats of the human being &amp; then proposed methodology applies for Detection &amp; Classification of Cardiac Arrhythmia. Detection of Cardiac Arrhythmia using ECG signals allows us for easy &amp; reliable way with low cost solution to diagnose Arrhythmia in its prior early stage.</p>

scholarly journals Valproic Acid-Like Compounds Enhance and Prolong the Radiotherapy Effect on Breast Cancer by Activating and Maintaining Anti-Tumor Immune Function

2021 ◽  
Vol 12 ◽  
Author(s):  
Zuchao Cai ◽  
David Lim ◽  
Guochao Liu ◽  
Chen Chen ◽  
Liya Jin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Valproic Acid ◽  
Tumor Recurrence ◽  
Early Stage ◽  
Low Cost ◽  
Inhibit Tumor Growth ◽  
Tnf Α ◽  
M1 Phenotype ◽  
Ifn Γ ◽  
Concurrent Cancer

Inadequate sustained immune activation and tumor recurrence are major limitations of radiotherapy (RT), sustained and targeted activation of the tumor microenvironment can overcome this obstacle. Here, by two models of a primary rat breast cancer and cell co-culture, we demonstrated that valproic acid (VPA) and its derivative (HPTA) are effective immune activators for RT to inhibit tumor growth by inducing myeloid-derived macrophages and polarizing them toward the M1 phenotype, thus elevate the expression of cytokines such as IL-12, IL-6, IFN-γ and TNF-α during the early stage of the combination treatment. Meanwhile, activated CD8+ T cells increased, angiogenesis of tumors is inhibited, and the vasculature becomes sparse. Furthermore, it was suggested that VPA/HPTA can enhance the effects of RT via macrophage-mediated and macrophage-CD8+ T cell-mediated anti-tumor immunity. The combination of VPA/HPTA and RT treatment slowed the growth of tumors and prolong the anti-tumor effect by continuously maintaining the activated immune response. These are promising findings for the development of new effective, low-cost concurrent cancer therapy.

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