Publications by authors named "Huamin Li"

37 Publications

Two Birds with One Stone: Prelithiated Two-Dimensional Nanohybrids as High-Performance Anode Materials for Lithium-Ion Batteries.

ACS Appl Mater Interfaces 2022 Aug 1;14(31):35673-35681. Epub 2022 Aug 1.

Department of Materials Design and Innovation, University at Buffalo, The State University of New York, Buffalo, New York 14260, United States.

As an inexpensive and naturally abundant two-dimensional (2D) material, molybdenum disulfide (MoS) exhibits a high Li-ion storage capacity along with a low volume expansion upon lithiation, rendering it an alternative anode material for lithium-ion batteries (LIBs). However, the challenge of using MoS-based anodes is their intrinsically low electrical conductivity and unsatisfied cycle stability. To address the above issues, we have exploited a wet chemical technique and integrated MoS with highly conductive titanium carbide (TiC) MXene to form a 2D nanohybrid. The binary hybrids were then subjected to an -butyllithium (-Buli) treatment to induce both MoS deep phase transition and MXene surface functionality modulation simultaneously. We observed a substantial increase in 1T-phase MoS content and a clear suppression of -F-containing functional groups in MXene due to the prelithiation process enabled by the -Buli treatment. Such an approach not only increases the overall network conductivity but also improves Li-ion diffusion kinetics. As a result, the MoS/TiC composite with -Buli treatment delivered a high Li-ion storage capacity (540 mA h g at 100 mA g), outstanding cycle stability (up to 300 cycles), and excellent rate capability. This work provides an effective strategy for the structure-property engineering of 2D materials and sheds light on the rational design of high-performance LIBs using 2D-based anode materials.
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http://dx.doi.org/10.1021/acsami.2c07984DOI Listing
August 2022

Mechanism of In-Plane and Out-of-Plane Tribovoltaic Direct-Current Transport with a Metal/Oxide/Metal Dynamic Heterojunction.

ACS Appl Mater Interfaces 2022 Jan 6;14(2):2968-2978. Epub 2022 Jan 6.

Department of Mechanical and Aerospace Engineering, University at Buffalo, The State University of New York, Buffalo, New York 14260, United States.

Interfacial layer engineering has been demonstrated as an effective strategy for boosting power output in semiconductor-based dynamic direct-current (DC) generators, although the underlying mechanism of power enhancement remains obscure. Here, such ambiguity has been elucidated by comparing fundamental tribovoltaic DC output characteristics of prototypical metal-oxide-metal heterojunctions prepared by atomic-layer deposition (ALD) with a vertical (out-of-plane carrier transport through the interfacial layer) and a horizontal (in-plane carrier transport along the interfacial layer) configuration such that the influences from nonequilibrium electronic excitation and interfacial capacitive amplification can be individually tuned and investigated. It is found in the case of Al/TiO/Ti vertical configurations that the open-circuit voltage () increases linearly from -0.03 to -0.52 V as the thickness of titanium oxide () increases from 0 to 200 nm with a linear amplification coefficient of -2.31 mV nm, which is validated by a parallel-capacitor theoretical model with tribovoltaic electronic excitation. In contrast, the output with the horizontal configuration is ∼55 mV, where the potential difference is merely associated with the accumulation of surface charges and the subsequent charge rearrangement in the depletion region. Meanwhile, it is measured that the short-circuit current density () shows an initial increasing trend when increases, reaches its peak value at 0.21 A m at = 20 nm, and then decreases as increases further. From current-voltage (-) characterization, it is proposed that such DC output variation with an optimal interfacial layer thickness stems from the competition of amplified voltage and increased resistance with increasing interfacial layer thickness, with the main charge transport mechanism switching from quantum tunneling to thermionic emission/trap-assisted transport. In contrast, tribovoltaic excitation is proven to be significantly weaker when a wide band-gap insulator (AlO) is involved. The elucidation of the fundamental mechanism of power enhancement by the interfacial layer in this work is of great significance in providing instructional direction for the development and optimization of high-performance DC nanogenerators.
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http://dx.doi.org/10.1021/acsami.1c22438DOI Listing
January 2022

Mechanism, Material, Design, and Implementation Principle of Two-Dimensional Material Photodetectors.

Nanomaterials (Basel) 2021 Oct 12;11(10). Epub 2021 Oct 12.

Department of Electrical Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260, USA.

Two-dimensional (2D) materials may play an important role in future photodetectors due to their natural atom-thin body thickness, unique quantum confinement, and excellent electronic and photoelectric properties. Semimetallic graphene, semiconductor black phosphorus, and transition metal dichalcogenides possess flexible and adjustable bandgaps, which correspond to a wide interaction spectrum ranging from ultraviolet to terahertz. Nevertheless, their absorbance is relatively low, and it is difficult for a single material to cover a wide spectrum. Therefore, the combination of phototransistors based on 2D hybrid structures with other material platforms, such as quantum dots, organic materials, or plasma nanostructures, exhibit ultra-sensitive and broadband optical detection capabilities that cannot be ascribed to the individual constituents of the assembly. This article provides a comprehensive and systematic review of the recent research progress of 2D material photodetectors. First, the fundamental detection mechanism and key metrics of the 2D material photodetectors are introduced. Then, the latest developments in 2D material photodetectors are reviewed based on the strategies of photocurrent enhancement. Finally, a design and implementation principle for high-performance 2D material photodetectors is provided, together with the current challenges and future outlooks.
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http://dx.doi.org/10.3390/nano11102688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8537528PMC
October 2021

Screening of gamma-aminobutyric acid-producing lactic acid bacteria and the characteristic of glutamate decarboxylase from Levilactobacillus brevis F109-MD3 isolated from kimchi.

J Appl Microbiol 2022 Mar 4;132(3):1967-1977. Epub 2021 Oct 4.

Department of Food Engineering, Mokpo National University, Jeonnam, Republic of Korea.

Aims: This study aimed to screen the γ-aminobutyric acid (GABA)-producing lactic acid bacteria (LAB) from kimchi, and investigate the glutamate decarboxylase (GAD) activity of the highest GABA-producing strain.

Methods And Results: Seven strains of LAB were screened from kimchi with GABA-producing activity. Strain Levilactobacillus brevis F109-MD3 showed the highest GABA-producing ability. It produced GABA at a concentration of 520 mmol l with a 97.4% GABA conversion rate in MRS broth containing 10% monosodium glutamate for 72 h. The addition of pyridoxal 5'-phosphate had no significant effect on the GAD activity of L. brevis F109-MD3. The optimal pH range of GAD was 3.0-5.0 and the optimal temperature was 65°C. The D value of GAD at 50, 60 and 70°C was 7143, 971 and 124 min respectively and Z value was 11.36°C.

Conclusions: Seven strains isolated from kimchi, especially F109-MD3, showed high GABA-production ability even in the high concentrations of MSG at 7.5% and 10%. The GAD activity showed an effective broad pH range and higher optimal temperature.

Significance And Impact Of The Study: These seven strains could be potentially useful for food-grade GABA production and the development of healthy foods.
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http://dx.doi.org/10.1111/jam.15306DOI Listing
March 2022

Numerical simulation of realistic top coal caving intervals under different top coal thicknesses in longwall top coal caving working face.

Sci Rep 2021 06 24;11(1):13254. Epub 2021 Jun 24.

School of Energy Science and Engineering, Henan Polytechnic University, Jiaozuo, 454003, Henan, China.

In the process of longwall top coal caving, the selection of the top coal caving interval along the advancing direction of the working face has an important effect on the top coal recovery. To explore a realistic top coal caving interval of the longwall top coal caving working face, longwall top coal caving panel 8202 in the Tongxin Coal Mine is used as an example, and 30 numerical simulation models are established by using Continuum-based Distinct Element Method simulation software to study the top coal recovery with 4.0 m, 8.0 m, 12.0 m, 16.0 m, 20.0 m and 24.0 m top coal thicknesses and 0.8 m, 1.0 m, 1.2 m, 1.6 m and 2.4 m top coal caving intervals. The results show that with an increase in the top coal caving interval, the single top coal caving amount increases. The top coal recovery is the highest with a 0.8 m top coal caving interval when the thickness of the top coal is 4.0 m, and it is the highest with a 1.2 m top coal caving interval when the coal seam thickness is greater than 4.0 m. These results provide a reference for the selection of a realistic top coal caving interval in thick coal seam caving mining.
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http://dx.doi.org/10.1038/s41598-021-92624-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225838PMC
June 2021

Two-Dimensional Cold Electron Transport for Steep-Slope Transistors.

ACS Nano 2021 Mar 11;15(3):5762-5772. Epub 2021 Mar 11.

Department of Electrical Engineering, University at Buffalo, The State University of New York, Buffalo, New York 14260, United States.

Room-temperature Fermi-Dirac electron thermal excitation in conventional three-dimensional (3D) or two-dimensional (2D) semiconductors generates hot electrons with a relatively long thermal tail in energy distribution. These hot electrons set a fundamental obstacle known as the "Boltzmann tyranny" that limits the subthreshold swing (SS) and therefore the minimum power consumption of 3D and 2D field-effect transistors (FETs). Here, we investigated a graphene (Gr)-enabled cold electron injection where the Gr acts as the Dirac source to provide the cold electrons with a localized electron density distribution and a short thermal tail at room temperature. These cold electrons correspond to an electronic refrigeration effect with an effective electron temperature of ∼145 K in the monolayer MoS, which enables the transport factor lowering and thus the steep-slope switching (across for three decades with a minimum SS of 29 mV/decade at room temperature) for a monolayer MoS FET. Especially, a record-high sub-60-mV/decade current density (over 1 μA/μm) can be achieved compared to conventional steep-slope technologies such as tunneling FETs or negative capacitance FETs using 2D or 3D channel materials. Our work demonstrates the potential of a 2D Dirac-source cold electron transistor as a steep-slope transistor concept for future energy-efficient nanoelectronics.
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http://dx.doi.org/10.1021/acsnano.1c01503DOI Listing
March 2021

Plasma treated graphene FET sensor for the DNA hybridization detection.

Talanta 2021 Feb 18;223(Pt 2):121766. Epub 2020 Oct 18.

School of Physics and Electronics, Shandong Normal University, Jinan, 250014, People's Republic of China; Department of Electrical Engineering, University at Buffalo North Campus, Buffalo, NY, 14260, USA. Electronic address:

Room-temperature plasma treated graphene based FET was firstly proposed for the DNA hybridization detection. Affinity and electrical properties of the graphene based DNA-FET sensor were studied and improved benefits from the surface modification. The facile room-temperature Ar plasma easily removes residues from the graphene surface and changes the hydrophilic properties of graphene, which is important for our solution gated DNA-FET sensor. Limit of the detection of below 10 aM is obtained in our experiment. Especially, DNA concentration (C)/the amount of net drain current (ΔI) and the negative shift in the V value of the GFET sensor with the plasma treated 30 s are all improved compared with that without treatment. It shows that the easily plasma treatment of the graphene surface can be used for the solution gated FET sensor.
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http://dx.doi.org/10.1016/j.talanta.2020.121766DOI Listing
February 2021

Verification of a novel glyceraldehyde-3-phosphate dehydrogenase capable of histamine degradation and its preliminary application in wine production.

Food Sci Biotechnol 2020 Dec 31;29(12):1719-1726. Epub 2020 Oct 31.

School of Food Engineering, Ludong University, Yantai, 264025 Shandong People's Republic of China.

The search for enzymes with histamine-degrading activity is of great interest, since it has great potential in the way of solving the problem of high histamine levels in food. In this study, the gene of a novel histamine-degrading enzyme, i.e., glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from was cloned and successfully expressed in DH5α, with the recombinant host determined as histamine-degrading active. The recombinant GAPDH was then purified to homogeneity by ammonium sulfate fraction and gel filtration. The optimum pH and temperature were 5.5 and 40 °C and it was strongly resistant to SO and ethanol. Afterwards, the histamine degradative activity of partially purified GAPDH in actual wine environments (grape and cherry wines) was examined by incubating the enzymes in the middle, near the end and completion of malolactic fermentation, and histamine in the corresponding contaminated wines was decreased by 36.8-52.4%, 59.6-66.9% and 83.1-85.5%, respectively.
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http://dx.doi.org/10.1007/s10068-020-00838-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708551PMC
December 2020

Hereditary angioedema: Long-term prophylactic treatment.

Authors:
Huamin Henry Li

Allergy Asthma Proc 2020 11;41(Suppl 1):S35-S37

From the Institute for Asthma and Allergy, Chevy Chase, Maryland.

Hereditary Angioedema (HAE) is a potentially life-threatening condition. With episodic, unpredictable swelling, HAE negatively affect the quality of life for those affected individuals. To reduce the morbidity and mortality of HAE are the primary goal for the disease management. In addition to have access to therapeutic drugs for their acute HAE attacks, many patients require long term prophylaxis (LTP) to reduce their attack frequency and severity. Preventing HAE attack by regular administration of medicine has become an important part of HAE disease management. Over the past few years, growing number of therapeutic options for the HAE LTP have made it possible for physicians to choose the most appropriate and effective treatment for individual patients. C1 INH concentrate and plasma kallikrein inhibitors (IV or SC) have largely replaced the oder modality of treatment consisting different androgen derivatives or antifibrinolytics. Additional options, such as oral kallikrein inhibitor, antisense RNA/plasma kallikrein, anti-Factor 12a, bradykinin receptor blocker or future gene therapy are under clinical investigation. The significant cost and the uncertainty of its long term safety may be the primary limiting factors for its clinical application. The limited data for young children and pregnant women pose additional challenge for physicians to assess the risk and benefit when considering LTP treatment.
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http://dx.doi.org/10.2500/aap.2020.41.200092DOI Listing
November 2020

Diode-Like Selective Enhancement of Carrier Transport through Metal-Semiconductor Interface Decorated by Monolayer Boron Nitride.

Adv Mater 2020 Sep 28;32(36):e2002716. Epub 2020 Jul 28.

Department of Electrical Engineering, University at Buffalo, The State University of New York, Buffalo, NY, 14260, USA.

2D semiconductors such as monolayer molybdenum disulfide (MoS ) are promising material candidates for next-generation nanoelectronics. However, there are fundamental challenges related to their metal-semiconductor (MS) contacts, which limit the performance potential for practical device applications. In this work, 2D monolayer hexagonal boron nitride (h-BN) is exploited as an ultrathin decorating layer to form a metal-insulator-semiconductor (MIS) contact, and an innovative device architecture is designed as a platform to reveal a novel diode-like selective enhancement of the carrier transport through the MIS contact. The contact resistance is significantly reduced when the electrons are transported from the semiconductor to the metal, but is barely affected when the electrons are transported oppositely. A concept of carrier collection barrier is proposed to interpret this intriguing phenomenon as well as a negative Schottky barrier height obtained from temperature-dependent measurements, and the critical role of the collection barrier at the drain end is shown for the overall transistor performance.
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http://dx.doi.org/10.1002/adma.202002716DOI Listing
September 2020

Effect of Saccharomyces cerevisiae, Torulaspora delbrueckii and malolactic fermentation on fermentation kinetics and sensory property of black raspberry wines.

Food Microbiol 2020 Oct 26;91:103551. Epub 2020 May 26.

School of Food Engineering, Ludong University, Yantai, Shandong, 264025, PR China; Institute of Bionanotechnology, Ludong University, Yantai, Shandong, 264025, PR China. Electronic address:

Alcoholic fermentation (AF) and malolactic fermentation (MLF) both have significant influence on the production of black raspberry wine. In this study, three microbes associated with AF and MLF including S. cerevisiae, T. delbrueckii and O. oeni were used to investigate their combined effect on basic compositional, volatile and sensory property of black raspberry wine, and four fermentation trials including single S. cerevisiae inoculation plus spontaneous MLF (BSU) and controlled MLF with O. oeni (BSO), sequential culture of T. delbrueckii and S. cerevisiae plus spontaneous MLF (BTSU) and controlled MLF (BTSO) were tested and compared. Fermentation results showed MLF in BSU, BSO and BTSO were successful, with respective period of 40, 25 and 23 days, whereas a stuck MLF occurred in BTSU. Volatile compounds were determined by HS-GC-IMS method, with a total of 45 aromas identified. BTSO was distinguished by a significant higher signal intensity of many fruity esters and a lower production of several alcohols and terpenes, which was in agreement with its perception result of strong 'fruity' and slight note of 'solvent' and 'herbaceous' during quantitative descriptive analysis. On the contrary, BSU was found to reinforce the synthesis of most detected volatiles, resulting in the enhancement of both beneficial and off-flavour compounds, therefore scoring lower in the 'global aroma' descriptor. Principal component analysis showed BSU and BSO were similar in the volatile composition, whereas BTSO was quite different. Overall, BTSO had greater potential to be used in the production of black raspberry wine.
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http://dx.doi.org/10.1016/j.fm.2020.103551DOI Listing
October 2020

Enrichment experiment of ventilation air methane (0.5%) by the mechanical tower.

Sci Rep 2020 Apr 29;10(1):7276. Epub 2020 Apr 29.

College of Computer Science and Technology, Nanjing Forestry University, 210037, Nanjing, China.

Methane is one of the most important gases leading to the earth's air pollution. Ventilation air methane(VAM) is an important part of the gas discharged into the atmosphere. The volume concentration of methane is generally less than 0.5% in coal mines. Recycling low concentration is facing challenges. To explore the law of low concentration methane enrichment, the enrichment tower for methane was designed and manufactured. The experiment was divided into two types - free diffusion and weak eddy enrichment, and eight kinds of low concentration gas experimental program. Under free diffusion conditions, the maximum methane concentration of the top (middle) tower is 0.64% (0.53%). In the condition of weak eddy field, the maximum methane concentration is 0.67% (0.69%) in the top (middle) tower. The effect of methane enrichment in the weak eddy field is obvious. Methane enrichment method under the eddy current field can greatly increase methane enrichment efficiency and achieve the goal of CMM (coal mine methane) power generation.
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http://dx.doi.org/10.1038/s41598-020-63698-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7190646PMC
April 2020

Enhanced carrier transport by transition metal doping in WS field effect transistors.

Nanoscale 2020 Sep 24;12(33):17253-17264. Epub 2020 Apr 24.

Department of Electrical Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260, USA.

High contact resistance is one of the primary concerns for electronic device applications of two-dimensional (2D) layered semiconductors. Here, we explore the enhanced carrier transport through metal-semiconductor interfaces in WS field effect transistors (FETs) by introducing a typical transition metal, Cu, with two different doping strategies: (i) a "generalized" Cu doping by using randomly distributed Cu atoms along the channel and (ii) a "localized" Cu doping by adapting an ultrathin Cu layer at the metal-semiconductor interface. Compared to the pristine WS FETs, both the generalized Cu atomic dopant and localized Cu contact decoration can provide a Schottky-to-Ohmic contact transition owing to the reduced contact resistances by 1-3 orders of magnitude, and consequently elevate electron mobilities by 5-7 times. Our work demonstrates that the introduction of transition metal can be an efficient and reliable technique to enhance the carrier transport and device performance in 2D TMD FETs.
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http://dx.doi.org/10.1039/d0nr01573cDOI Listing
September 2020

Comparison of fermentation behaviors and properties of raspberry wines by spontaneous and controlled alcoholic fermentations.

Food Res Int 2020 02 21;128:108801. Epub 2019 Nov 21.

School of Food Engineering, Ludong University, Yantai, Shandong 264025, PR China; Institute of Food Science and Engineering, Yantai University, Yantai, Shandong 264005, PR China. Electronic address:

Torulaspora delbrueckii is a widely studied non-Saccharomyces yeast, described as having a positive impact on the organoleptic quality of wines, however, little is known about its impact on the production of raspberry wine. In this study, we compared combined use of S. cerevisiae/T. delbrueckii pair, i.e., in sequential inoculation (RT) and co-fermentation (RC) modes, with spontaneous fermentation (RU) and single S. cerevisiae inoculation (RS), on various properties of raspberry wine including fermentation behaviors (using yeast counts and next-generation sequencing method), basic composition (by OIV, 2019), volatile profile (using headspace-gas chromatography-ion mobility spectrometry), sensory property (by quantitative descriptive analyses) and biogenic amine levels. All the alcoholic fermentations were completed within 9 days; T. delbrueckii was inhibited by S. cerevisiae in the co-culture; and Saccharomyces and Mrakia were the most abundant species in RU. A total of 40 aromas was identified, with RT abundant in volatile esters, ketones and terpenes and others showing relatively lower intensities. During sensory evaluation, RT was characterized by 'fruity' and 'sweet' notes; RC was notable for a high 'floral' attribute; RU scored the highest in 'pungent' and RS showed intermedium intensities for most descriptors. Partial least squares regression showed the relationship between aromas and sensory descriptors. As for biogenic amine, RU contained the highest total amount and RS had the least. Overall, RT had greater potential to be used in the production of raspberry wine.
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http://dx.doi.org/10.1016/j.foodres.2019.108801DOI Listing
February 2020

Suspended CNT-Based FET sensor for ultrasensitive and label-free detection of DNA hybridization.

Biosens Bioelectron 2019 Jul 3;137:255-262. Epub 2019 May 3.

School of Physics and Electronics, Shandong Normal University, Jinan, 250014, People's Republic of China; Institute of Materials and Clean Energy, Shandong Normal University, Jinan, 250014, People's Republic of China. Electronic address:

A suspended carbon nanotube (SCNT)-based field effective transistor (SCNT-FET), which was fabricated by utilizing the surface tension of liquid silver to suspend a CNT between two Pd electrodes, was proposed for the detection of DNA hybridization. Benefits from the separation between the CNT and the substrates could be observed; namely, the conductivity of a SCNT-FET was much higher (two orders of magnitude) than that of a FET based on an unsuspended CNT and about 50% sensing surface of CNT was freed from substrate. The Slater-Koster tight-binding method was adopted for geometry optimization and transport property calculation of the SCNT bound with DNA. The result showed that the conductance (G = 1/R) of the SCNT decreased in order with the binding of single-stranded DNA (SSDNA, probe DNA) and double-stranded DNA (DSDNA) and that the ability of DSDNA to weaken the conductivity of the SCNT was several times higher than that of SSDNA. SEM and Raman spectroscopy were used to demonstrate that DNA could be bound successfully onto the SCNT using a 1-pyrenebutanoic acid succinimidyl ester (PBASE) as a linkage. Ultra-high sensitivity detection of DNA [with a limit of detection (LOD) as low as 10 aM] was obtained using such an SCNT-FET, which showed a lower value than that of a previously reported FET DNA biosensor whose sensing materials were in direct contact with the substrate.
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http://dx.doi.org/10.1016/j.bios.2019.04.054DOI Listing
July 2019

Ex vivo Dynamics of Human Glioblastoma Cells in a Microvasculature-on-a-Chip System Correlates with Tumor Heterogeneity and Subtypes.

Adv Sci (Weinh) 2019 Apr 10;6(8):1801531. Epub 2019 Feb 10.

Department of Biomedical Engineering Yale University New Haven CT 06520 USA.

The perivascular niche (PVN) plays an essential role in brain tumor stem-like cell (BTSC) fate control, tumor invasion, and therapeutic resistance. Here, a microvasculature-on-a-chip system as a PVN model is used to evaluate the ex vivo dynamics of BTSCs from ten glioblastoma patients. BTSCs are found to preferentially localize in the perivascular zone, where they exhibit either the lowest motility, as in quiescent cells, or the highest motility, as in the invasive phenotype, with migration over long distance. These results indicate that PVN is a niche for BTSCs, while the microvascular tracks may serve as a path for tumor cell migration. The degree of colocalization between tumor cells and microvessels varies significantly across patients. To validate these results, single-cell transcriptome sequencing (10 patients and 21 750 single cells in total) is performed to identify tumor cell subtypes. The colocalization coefficient is found to positively correlate with proneural (stem-like) or mesenchymal (invasive) but not classical (proliferative) tumor cells. Furthermore, a gene signature profile including PDGFRA correlates strongly with the "homing" of tumor cells to the PVN. These findings demonstrate that the model can recapitulate in vivo tumor cell dynamics and heterogeneity, representing a new route to study patient-specific tumor cell functions.
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http://dx.doi.org/10.1002/advs.201801531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468969PMC
April 2019

Indirect comparison of intravenous vs. subcutaneous C1-inhibitor placebo-controlled trials for routine prevention of hereditary angioedema attacks.

Allergy Asthma Clin Immunol 2019 7;15:13. Epub 2019 Mar 7.

AMF Consulting, Inc., Los Angeles, CA USA.

Introduction: For prophylaxis of hereditary angioedema (HAE) attacks, replacement therapy with human C1-inhibitor (C1-INH) treatment is approved and available as intravenous [C1-INH(IV)] (Cinryze) and subcutaneous [C1-INH(SC)] HAEGARDA preparations. In the absence of a head-to-head comparative study of the two treatment modalities, an indirect comparison of data from 2 independent but similar clinical trials was undertaken.

Methods: Two similar randomized, double-blind, placebo-controlled, crossover studies were identified which evaluated either C1-INH(SC) (COMPACT; NCT01912456; 16 weeks) or C1-INH(IV) (CHANGE; NCT01005888; 14 weeks) vs. placebo (on-demand treatment only) for routine prevention of HAE attacks. Individual patient data from each trial were used to conduct an indirect comparison of treatment effects. Attack reductions (absolute and percent of mean/median number of monthly HAE attacks reduction over placebo) were compared between the two C1-INH formulations at approved/recommended doses: C1-INH(SC) 60 IU/kg twice weekly (n = 45) and 1000 U of C1-INH(IV) twice weekly (n = 22). Point estimates were adjusted using mixed and quantile regression models that controlled for study design.

Results: The absolute mean monthly numbers of HAE attack reductions were 3.6 (95% CI 2.9, 4.2) for C1-INH(SC) 60 IU/kg vs. placebo and 2.3 (1.4, 3.3) for C1-INH(IV) vs. placebo; between-product difference, 1.3 (0.1, 2.4; = 0.034). The mean percent reduction in monthly attack rate was significantly greater with C1-INH(SC) as compared with C1-INH(IV) (84% vs. 51%; < 0.001). The percentages of subjects experiencing ≥ 50%, ≥ 70%, and ≥ 90% reductions in monthly HAE attack rates versus placebo were significantly higher with C1-INH(SC) 60 IU/kg as compared to C1-INH(IV) 1000 U (≥ 50% reduction: 91% vs. 50%, odds ratio [OR] = 10.33, = 0.003; ≥ 70% reduction: 84% vs. 46%, OR = 6.19,  = 0.005; ≥ 90% reduction: 57% vs. 18%, OR = 6.04,  = 0.007).

Conclusion: Within the limitations of an indirect study comparison, this analysis suggests greater attack reduction with twice-weekly C1-INH(SC) 60 IU/kg as compared to twice-weekly C1-INH(IV) 1000 U for the routine prevention of HAE attacks.
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http://dx.doi.org/10.1186/s13223-019-0328-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6407188PMC
March 2019

LASSO‑based Cox‑PH model identifies an 11‑lncRNA signature for prognosis prediction in gastric cancer.

Mol Med Rep 2018 Dec 22;18(6):5579-5593. Epub 2018 Oct 22.

Department of General Surgery, Yulin Xingyuan Hospital, Yulin, Shaanxi 719000, P.R. China.

The present study aimed to identify a long non‑coding (lnc) RNAs‑based signature for prognosis assessment in gastric cancer (GC) patients. By integrating gene expression data of GC and normal samples from the National Center for Biotechnology Information Gene Expression Omnibus, the EBI ArrayExpress and The Cancer Genome Atlas (TCGA) repositories, the common RNAs in Genomic Spatial Event (GSE) 65801, GSE29998, E‑MTAB‑1338, and TCGA set were screened and used to construct a weighted correlation network analysis (WGCNA) network for mining GC‑related modules. Consensus differentially expressed RNAs (DERs) between GC and normal samples in the four datasets were screened using the MetaDE method. From the overlapped lncRNAs shared by preserved WGCNA modules and the consensus DERs, an lncRNAs signature was obtained using L1‑penalized (lasso) Cox‑proportional hazard (PH) model. LncRNA‑mRNA networks were constructed for these signature lncRNAs, followed by functional annotation. A total of 14,824 common mRNAs and 2,869 common lncRNAs were identified in the 4 sets and 5 GC‑associated WGCNA modules were preserved across all sets. MetaDE method identified 1,121 consensus DERs. A total of 50 lncRNAs were shared by preserved WGCNA modules and the consensus DERs. Subsequently, an 11‑lncRNA signature was identified by LASSO‑based Cox‑PH model. The lncRNAs signature‑based risk score could divide patients into 2 risk groups with significantly different overall survival and recurrence‑free survival times. The predictive capability of this signature was verified in an independent set. These signature lncRNAs were implicated in several biological processes and pathways associated with the immune response, the inflammatory response and cell cycle control. The present study identified an 11‑lncRNA signature that could predict the survival rate for GC.
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http://dx.doi.org/10.3892/mmr.2018.9567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236314PMC
December 2018

Randomized algorithms for distributed computation of principal component analysis and singular value decomposition.

Adv Comput Math 2018 Oct 19;44(5):1651-1672. Epub 2018 Mar 19.

Facebook Artificial Intelligence Research, 1 Facebook Way, Menlo Park, CA 94025.

Randomized algorithms provide solutions to two ubiquitous problems: (1) the distributed calculation of a principal component analysis or singular value decomposition of a highly rectangular matrix, and (2) the distributed calculation of a low-rank approximation (in the form of a singular value decomposition) to an arbitrary matrix. Carefully honed algorithms yield results that are uniformly superior to those of the stock, deterministic implementations in Spark (the popular platform for distributed computation); in particular, whereas the stock software will without warning return left singular vectors that are far from numerically orthonormal, a significantly burnished randomized implementation generates left singular vectors that are numerically orthonormal to nearly the machine precision.
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http://dx.doi.org/10.1007/s10444-018-9600-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415723PMC
October 2018

Long-term prophylaxis therapy in patients with hereditary angioedema with C1 inhibitor deficiency.

Ann Allergy Asthma Immunol 2018 12 27;121(6):673-679. Epub 2018 Jul 27.

Asthma and Allergy Associates PC, Colorado Springs, Colorado.

Objective: To review the criteria for long-term prophylaxis therapy in patients with hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE), describe how these criteria have evolved over time, and anticipate how criteria may change in the future with the availability of new C1-INH-HAE treatment options.

Data Sources: Treatment guidelines, consensus statements, and expert reviews.

Study Selections: Manuscripts that described long-term prophylaxis therapy in patients with C1-INH-HAE were selected.

Results: Historically, patients with C1-INH-HAE were considered to be candidates for long-term prophylaxis therapy if they had at least 1 attack per month, had at least 5 days of disability per month because of C1-INH-HAE, or did not sufficiently respond to on-demand treatment. More recently, guidelines and reviews state that thresholds of number of attacks or days of disability are arbitrary and that treatment plans should be individualized to the patient's needs. Furthermore, all patients should have a comprehensive management plan that is reviewed periodically and should have at least 2 doses of on-demand treatment available. Prophylaxis therapy should be discussed as a potential treatment option for each patient; however, the decision for its use will depend on the patient's individual needs and the course of their symptoms.

Conclusion: The criteria for long-term prophylaxis therapy in C1-INH-HAE have changed with the recognition that treatments should be individualized to the patient's needs and with the availability of new medications that have more favorable benefit-risk profiles, are easier to use, and improve patients' quality of life.
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http://dx.doi.org/10.1016/j.anai.2018.07.025DOI Listing
December 2018

Hereditary angioedema from the patient's perspective: A follow-up patient survey.

Allergy Asthma Proc 2018 May;39(3):212-223

Department of Medicine, University of California San Diego, La Jolla, California.

Background: We conducted our first patient survey at the 2013 hereditary angioedema (HAE) patient summit and learned that, despite several novel therapies, the burden of disease was high.

Objective: To determine, from the patient's perspective, if any improvements in the current state of HAE care occurred over a two-year period between HAE patient summits.

Methods: A patient survey was conducted at the 2015 Hereditary Angioedema Association conference by using paper surveys that aimed at understanding the current state of HAE care. Questions included patient characteristics, burden of disease, and satisfaction with care and treatment options. Comparisons between patients with HAE with C1-inhibitor (HAE-C1INH) and patients with HAE with normal C1-inhibitor (HAE-nlC1INH), as well as between patients with HAE in 2013 and 2015, were performed by using χ2 tests.

Results: There were 232 surveys distributed, and 143 surveys were identified as complete for inclusion and analysis from patients with self-reported HAE. Most patients had type I or type II HAE (67.5% [n = 106]), with a smaller number of patients with HAE-nlC1INH (23.6% [n = 37]). In 2015, almost half of the patients with HAE-C1INH (47.1%) and 56.7% of the patients with HAE-nlC1INH experienced a delay of ≥10 years between initial symptoms and diagnosis. Among the patients with HAE-C1INH, 25% reported one or more attacks per week and another 48% reported experiencing one or more attacks per month (fewer than one attack per week). The patients with HAE-nlC1INH reported attacks more frequently than did the patients with HAE-C1INH (p = 0.002), with 59.5% who reported attacks at least once a week. Emergency care was reported one or more times per month in 5% of the patients with HAE-C1INH and in 24.3% of the patients with HAE-nlC1INH.

Conclusion: Similar to 2013, although significant progress has been made, there is still a high burden of disease that faces patients with HAE.
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http://dx.doi.org/10.2500/aap.2018.39.4123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5911511PMC
May 2018

Gating mass cytometry data by deep learning.

Bioinformatics 2017 Nov;33(21):3423-3430

Applied Mathematics Program.

Motivation: Mass cytometry or CyTOF is an emerging technology for high-dimensional multiparameter single cell analysis that overcomes many limitations of fluorescence-based flow cytometry. New methods for analyzing CyTOF data attempt to improve automation, scalability, performance and interpretation of data generated in large studies. Assigning individual cells into discrete groups of cell types (gating) involves time-consuming sequential manual steps, untenable for larger studies.

Results: We introduce DeepCyTOF, a standardization approach for gating, based on deep learning techniques. DeepCyTOF requires labeled cells from only a single sample. It is based on domain adaptation principles and is a generalization of previous work that allows us to calibrate between a target distribution and a source distribution in an unsupervised manner. We show that DeepCyTOF is highly concordant (98%) with cell classification obtained by individual manual gating of each sample when applied to a collection of 16 biological replicates of primary immune blood cells, even when measured across several instruments. Further, DeepCyTOF achieves very high accuracy on the semi-automated gating challenge of the FlowCAP-I competition as well as two CyTOF datasets generated from primary immune blood cells: (i) 14 subjects with a history of infection with West Nile virus (WNV), (ii) 34 healthy subjects of different ages. We conclude that deep learning in general, and DeepCyTOF specifically, offers a powerful computational approach for semi-automated gating of CyTOF and flow cytometry data.

Availability And Implementation: Our codes and data are publicly available at https://github.com/KlugerLab/deepcytof.git.

Contact: [email protected]

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btx448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5860171PMC
November 2017

Algorithm 971: An Implementation of a Randomized Algorithm for Principal Component Analysis.

ACM Trans Math Softw 2017 Jan;43(3)

Facebook, 1 Facebook Way, Menlo Park, CA 94025.

Recent years have witnessed intense development of randomized methods for low-rank approximation. These methods target principal component analysis and the calculation of truncated singular value decompositions. The present article presents an essentially black-box, foolproof implementation for Mathworks' MATLAB, a popular software platform for numerical computation. As illustrated via several tests, the randomized algorithms for low-rank approximation outperform or at least match the classical deterministic techniques (such as Lanczos iterations run to convergence) in basically all respects: accuracy, computational efficiency (both speed and memory usage), ease-of-use, parallelizability, and reliability. However, the classical procedures remain the methods of choice for estimating spectral norms and are far superior for calculating the least singular values and corresponding singular vectors (or singular subspaces).
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http://dx.doi.org/10.1145/3004053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5625842PMC
January 2017

Removal of batch effects using distribution-matching residual networks.

Bioinformatics 2017 Aug;33(16):2539-2546

Department of Pathology, Yale School of Medicine, New Haven, CT 06510, USA.

Motivation: Sources of variability in experimentally derived data include measurement error in addition to the physical phenomena of interest. This measurement error is a combination of systematic components, originating from the measuring instrument and random measurement errors. Several novel biological technologies, such as mass cytometry and single-cell RNA-seq (scRNA-seq), are plagued with systematic errors that may severely affect statistical analysis if the data are not properly calibrated.

Results: We propose a novel deep learning approach for removing systematic batch effects. Our method is based on a residual neural network, trained to minimize the Maximum Mean Discrepancy between the multivariate distributions of two replicates, measured in different batches. We apply our method to mass cytometry and scRNA-seq datasets, and demonstrate that it effectively attenuates batch effects.

Availability And Implementation: our codes and data are publicly available at https://github.com/ushaham/BatchEffectRemoval.git.

Contact: [email protected]

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btx196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5870543PMC
August 2017

Prevention of Hereditary Angioedema Attacks with a Subcutaneous C1 Inhibitor.

N Engl J Med 2017 03;376(12):1131-1140

From Barts Health NHS Trust (H.L.) and St. John's Institute of Dermatology, Guy's Hospital (C.G.), London, and the Clinical Investigation and Research Unit, Royal Sussex County Hospital, Brighton (M.T.) - all in the United Kingdom; Ospedale Luigi Sacco-U.O. Medicina Generale, Milan (M.C.), and the Department of Internal Medicine, University of Catania, Catania (S.N.) - both in Italy; Department of Medicine and Pediatrics, Penn State Hershey Allergy, Asthma, and Immunology, Hershey (T. Craig), and CSL Behring, King of Prussia (D.B.-K., J.E., D.P.) - both in Pennsylvania; the Department of Dermatology, Johannes Gutenberg University Mainz, Mainz (K.B.), and CSL Behring, Marburg (H. Feuersenger, J.-P.L., T.M., I.P.) - both in Germany; Baker Allergy, Asthma and Dermatology Research Center, Portland, OR (J. Baker); Institute for Asthma and Allergy, Chevy Chase, MD (H.H.L.); Allergy and Immunology Unit, Chaim Sheba Medical Center, Tel Hashomer (A.R.), and Allergy and Immunology Unit, Tel Aviv Sourasky Medical Center, Tel Aviv (S.K.) - both in Israel; Clinical Research Center of Alabama, Birmingham (J. Bonner, J.A.); Department of Internal Medicine, Allergy Section Cincinnati, University of Cincinnati College of Medicine, Cincinnati (J.A.B.), and Toledo Institute of Clinical Research, Toledo (S.M.R.) - both in Ohio; Allergy Asthma Research Associates Research Center, Dallas (W.R.L.); Hungarian Angioedema Center, Third Department of Internal Medicine, Semmelweis University, Budapest (H. Farkas); the Department of Medicine, Immunology, and Allergy, Campbelltown Hospital, Campbelltown, NSW, Australia (C.H.K.); the Department of Clinical Immunology and Allergy, St. Michael's Hospital, Toronto (G.L.S.), Centre de Recherche Appliqué en Allergie de Québec, Quebec, QC (J.H.), McMaster University, Hamilton, ON (P.K.K.), Ottawa Allergy Research and University of Ottawa Medical School, Ottawa (W.Y.), and University of Alberta Hospital, Edmonton (B.R.) - all in Canada; Allergy and Asthma Clinical Research, Walnut Creek (J.J.), University of California, San Diego School of Medicine, La Jolla (M.R., B.L.Z.), and 705 W. La Veta Ave., Suite 101, Orange (D.S.L.) - all in California; Medical Research of Arizona, Scottsdale (M.E.M.); Hospital General Universitario Gregorio Marañón and Biomedical Research Network on Rare Diseases-U761, Institute for Health Research, Gregorio Marañón (M.L.B.), and the Allergy Department, Hospital La Paz Institute for Health Research, Biomedical Research Network on Rare Diseases (T. Caballero), Madrid, the Allergy Department, IIS Hospital Universitario La Fe, Valencia (M.D.H.), and Hospital Universitario Vall d'Hebron, Barcelona (M.G.) - all in Spain; Asthma and Allergy Association, Colorado Springs, CO (R.N.); Department of Internal Medicine, Virginia Commonwealth University, Richmond (L.B.S.); Spitalul Clinic Municipal, Cluj-Napoca, Romania (I.C.); Vital Prospects Clinical Research Institute, Tulsa, OK (I.H.); Institute of Clinical Immunology and Allergology, University Hospital, Hradec Kralove, Czech Republic (P.K.); Division of Rheumatology, Allergy, and Immunology, Massachusetts General Hospital, Boston (A.B.); and Marycliff Allergy Specialists, Spokane, WA (R.G.G.).

Background: Hereditary angioedema is a disabling, potentially fatal condition caused by deficiency (type I) or dysfunction (type II) of the C1 inhibitor protein. In a phase 2 trial, the use of CSL830, a nanofiltered C1 inhibitor preparation that is suitable for subcutaneous injection, resulted in functional levels of C1 inhibitor activity that would be expected to provide effective prophylaxis of attacks.

Methods: We conducted an international, prospective, multicenter, randomized, double-blind, placebo-controlled, dose-ranging, phase 3 trial to evaluate the efficacy and safety of self-administered subcutaneous CSL830 in patients with type I or type II hereditary angioedema who had had four or more attacks in a consecutive 2-month period within 3 months before screening. We randomly assigned the patients to one of four treatment sequences in a crossover design, each involving two 16-week treatment periods: either 40 IU or 60 IU of CSL830 per kilogram of body weight twice weekly followed by placebo, or vice versa. The primary efficacy end point was the number of attacks of angioedema. Secondary efficacy end points were the proportion of patients who had a response (≥50% reduction in the number of attacks with CSL830 as compared with placebo) and the number of times that rescue medication was used.

Results: Of the 90 patients who underwent randomization, 79 completed the trial. Both doses of CSL830, as compared with placebo, reduced the rate of attacks of hereditary angioedema (mean difference with 40 IU, -2.42 attacks per month; 95% confidence interval [CI], -3.38 to -1.46; and mean difference with 60 IU, -3.51 attacks per month; 95% CI, -4.21 to -2.81; P<0.001 for both comparisons). Response rates were 76% (95% CI, 62 to 87) in the 40-IU group and 90% (95% CI, 77 to 96) in the 60-IU group. The need for rescue medication was reduced from 5.55 uses per month in the placebo group to 1.13 uses per month in the 40-IU group and from 3.89 uses in the placebo group to 0.32 uses per month in the 60-IU group. Adverse events (most commonly mild and transient local site reactions) occurred in similar proportions of patients who received CSL830 and those who received placebo.

Conclusions: In patients with hereditary angioedema, the prophylactic use of a subcutaneous C1 inhibitor twice weekly significantly reduced the frequency of acute attacks. (Funded by CSL Behring; COMPACT EudraCT number, 2013-000916-10 , and ClinicalTrials.gov number, NCT01912456 .).
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http://dx.doi.org/10.1056/NEJMoa1613627DOI Listing
March 2017

Subcutaneous Icatibant for the Treatment of Hereditary Angioedema Attacks: Comparison of Home Self-Administration with Administration at a Medical Facility.

J Allergy Clin Immunol Pract 2017 Mar - Apr;5(2):442-447.e1. Epub 2016 Nov 3.

Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Mass.

Background: Hereditary angioedema (HAE) is a life-threatening disorder characterized by recurrent angioedema. Icatibant, a subcutaneous bradykinin-B2-receptor antagonist, is an effective on-demand therapy. Data outside the United States suggest that self-administration is tolerated and patient-preferred compared with administration by health care professionals at medical facilities (HCP-administration).

Objective: A prospective, multicenter study was conducted in the United States to compare icatibant self-administration and HCP-administration.

Methods: Subjects 18 years or older with type I or II HAE were recruited. The first 2 HAE attacks after enrollment were treated at medical facilities. Subjects were instructed by a health care professional on self-administration during icatibant treatment for the second HAE attack. Icatibant was self-administered for all subsequent attacks. For each treated HAE attack, efficacy, safety, and tolerability data were recorded.

Results: Nineteen patients with HAE received icatibant for 79 distinct HAE attacks. Mean attack duration was significantly shorter with self-administration (n = 50; 547 ± 510 minutes) than with HCP-administration (n = 29; 968 ± 717 minutes; P = .006). Mean time to treatment was significantly shorter with self-administration (143 ± 226 minutes) than with HCP-administration (361 ± 503 minutes; P < .0001). Shorter times to treatment were associated with shorter time from treatment to symptom resolution (r = 0.35; P = .02). Improvements in visual analog scale score and patient symptom score from pretreatment to 4 hours postinjection were comparable between self-administration and HCP-administration. There were no serious adverse events or discontinuations due to adverse events with self-administration or HCP-administration.

Conclusions: Icatibant self-administration shortened attack duration and time to treatment, with no difference in safety or local tolerability compared with HCP-administration. These findings support icatibant as an effective on-demand option for home-based treatment.
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http://dx.doi.org/10.1016/j.jaip.2016.09.023DOI Listing
November 2017

Self-administered C1 esterase inhibitor concentrates for the management of hereditary angioedema: usability and patient acceptance.

Authors:
Huamin Henry Li

Patient Prefer Adherence 2016 7;10:1727-37. Epub 2016 Sep 7.

Institute for Asthma and Allergy, Chevy Chase, MD, USA.

Hereditary angioedema (HAE) is a rare genetic disease characterized by episodic subcutaneous or submucosal swelling. The primary cause for the most common form of HAE is a deficiency in functional C1 esterase inhibitor (C1-INH). The swelling caused by HAE can be painful, disfiguring, and life-threatening. It reduces daily function and compromises the quality of life of affected individuals and their caregivers. Among different treatment strategies, replacement with C1-INH concentrates is employed for on-demand treatment of acute attacks and long-term prophylaxis. Three human plasma-derived C1-INH preparations are approved for HAE treatment in the US, the European Union, or both regions: Cinryze(®), Berinert(®), and Cetor(®); however, only Cinryze is approved for long-term prophylaxis. Postmarketing studies have shown that home therapy (self-administered or administered by a caregiver) is a convenient and safe option preferred by many HAE patients. In this review, we summarize the role of self-administered plasma-derived C1-INH concentrate therapy with Cinryze at home in the prophylaxis of HAE.
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http://dx.doi.org/10.2147/PPA.S86379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5019432PMC
September 2016

Etiology and treatment of hematological neoplasms: stochastic mathematical models.

Adv Exp Med Biol 2014 ;844:317-46

Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA,

Leukemias are driven by stemlike cancer cells (SLCC), whose initiation, growth, response to treatment, and posttreatment behavior are often "stochastic", i.e., differ substantially even among very similar patients for reasons not observable with present techniques. We review the probabilistic mathematical methods used to analyze stochastics and give two specific examples. The first example concerns a treatment protocol, e.g., for acute myeloid leukemia (AML), where intermittent cytotoxic drug dosing (e.g., once each weekday) is used with intent to cure. We argue mathematically that, if independent SLCC are growing stochastically during prolonged treatment, then, other things being equal, front-loading doses are more effective for tumor eradication than back loading. We also argue that the interacting SLCC dynamics during treatment is often best modeled by considering SLCC in microenvironmental niches, with SLCC-SLCC interactions occurring only among SLCC within the same niche, and we present a stochastic dynamics formalism, involving "Poissonization," applicable in such situations. Interactions at a distance due to partial control of total cell numbers are also considered. The second half of this chapter concerns chromosomal aberrations, lesions known to cause some leukemias. A specific example is the induction of a Philadelphia chromosome by ionizing radiation, subsequent development of chronic myeloid leukemia (CML), CML treatment, and treatment outcome. This time evolution involves a coordinated sequence of > 10 steps, each stochastic in its own way, at the subatomic, molecular, macromolecular, cellular, tissue, and population scales, with corresponding time scales ranging from picoseconds to decades. We discuss models of these steps and progress in integrating models across scales.
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http://dx.doi.org/10.1007/978-1-4939-2095-2_16DOI Listing
April 2015

Repopulation of interacting tumor cells during fractionated radiotherapy: stochastic modeling of the tumor control probability.

Med Phys 2013 Dec;40(12):121716

London Health Sciences Center, London, Ontario N6A 5W9, Canada.

Purpose: Optimal treatment planning for fractionated external beam radiation therapy requires inputs from radiobiology based on recent thinking about the "five Rs" (repopulation, radiosensitivity, reoxygenation, redistribution, and repair). The need is especially acute for the newer, often individualized, protocols made feasible by progress in image guided radiation therapy and dose conformity. Current stochastic tumor control probability (TCP) models incorporating tumor repopulation effects consider "stem-like cancer cells" (SLCC) to be independent, but the authors here propose that SLCC-SLCC interactions may be significant. The authors present a new stochastic TCP model for repopulating SLCC interacting within microenvironmental niches. Our approach is meant mainly for comparing similar protocols. It aims at practical generalizations of previous mathematical models.

Methods: The authors consider protocols with complete sublethal damage repair between fractions. The authors use customized open-source software and recent mathematical approaches from stochastic process theory for calculating the time-dependent SLCC number and thereby estimating SLCC eradication probabilities. As specific numerical examples, the authors consider predicted TCP results for a 2 Gy per fraction, 60 Gy protocol compared to 64 Gy protocols involving early or late boosts in a limited volume to some fractions.

Results: In sample calculations with linear quadratic parameters α = 0.3 per Gy, α∕β = 10 Gy, boosting is predicted to raise TCP from a dismal 14.5% observed in some older protocols for advanced NSCLC to above 70%. This prediction is robust as regards: (a) the assumed values of parameters other than α and (b) the choice of models for intraniche SLCC-SLCC interactions. However, α = 0.03 per Gy leads to a prediction of almost no improvement when boosting.

Conclusions: The predicted efficacy of moderate boosts depends sensitively on α. Presumably, the larger values of α are the ones appropriate for individualized treatment protocols, with the smaller values relevant only to protocols for a heterogeneous patient population. On that assumption, boosting is predicted to be highly effective. Front boosting, apart from practical advantages and a possible advantage as regards iatrogenic second cancers, also probably gives a slightly higher TCP than back boosting. If the total number of SLCC at the start of treatment can be measured even roughly, it will provide a highly sensitive way of discriminating between various models and parameter choices. Updated mathematical methods for calculating repopulation allow credible generalizations of earlier results.
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http://dx.doi.org/10.1118/1.4829495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3843751PMC
December 2013

Genetic diversity of Pleurotus pulmonarius revealed by RAPD, ISSR, and SRAP fingerprinting.

Curr Microbiol 2014 Mar 17;68(3):397-403. Epub 2013 Nov 17.

Institute of Plant and Environment Protection, Beijing Academy of Agriculture and Forestry Science, Beijing, 100097, China.

Pleurotus pulmonarius is one of the most widely cultivated and popular edible fungi in the genus Pleurotus. Three molecular markers were used to analyze the genetic diversity of 15 Chinese P. pulmonarius cultivars. In total, 21 random amplified polymorphic DNA (RAPD), 20 inter-simple sequence repeat (ISSR), and 20 sequence-related amplified polymorphism (SRAP) primers or primer pairs were selected for generating data based on their clear banding profiles produced. With the use of these RAPD, ISSR, and SRAP primers or primer pairs, a total of 361 RAPD, 283 ISSR, and 131 SRAP fragments were detected, of which 287 (79.5 %) RAPD, 211 (74.6 %) ISSR, and 98 (74.8 %) SRAP fragments were polymorphic. Unweighted Pair-Group Method with Arithmetic Mean (UPGMA) trees of these three methods were structured similarly, grouping the 15 tested strains into four clades. Subsequently, visual DNA fingerprinting and cluster analysis were performed to evaluate the resolving power of the combined RAPD, ISSR, and SRAP markers in the differentiation among these strains. The results of this study demonstrated that each method above could efficiently differentiate P. pulmonarius cultivars and could thus be considered an efficient tool for surveying genetic diversity of P. pulmonarius.
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http://dx.doi.org/10.1007/s00284-013-0489-0DOI Listing
March 2014
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