bluuebunny/crossref_metadata_2025 huggingface dataset:
ANALISIS NERACA AIR PADA SUB DAERAH ALIRAN SUNGAI CODE YOGYAKARTA
Authors: Pradana Alvin , Hendrasari Ratna Septi
Published: April 2021

Abstract Water is one of the sources of human life. Population growth continues to increase and results in higher utilization of water sources. This will certainly affect the availability of water in the city of Yogyakarta. Water balance is a comparison between the water availability potential and the water demand of a place in a certain period. Water balance analysis is useful for knowing the amount of excess water (surplus) or lack of water (deficit) so that water use can be managed as well as possible. The calculation was done by analyzing the 10-year rainfall data using the Thiessen Polygon method to obtain the mean rainfall value. The available debit was calculated using the F.J. Mock method. The dependable discharge was calculated with 80% reliability from the 10-year debit data. The debit data was sorted from the largest to the smallest value, so that a probability value of 80% was obtained from the interpolation of the data sequence. Water demand was calculated based on the irrigation planning standard (KP-01). The results of the study show that the average water availability in the sub-watershed of Code River Yogyakarta was 527.92lt/sec. Based on the results of the analysis, the highest water deficit occurred in the first October at 278.40 l/sec and the lowest deficit was in the second July at 73.01 l/sec. However, the availability of water in certain months was quite abundant. Therefore, it is necessary to do a special study so that water is not wasted and can be used to cover water shortages in dry months. Keywords: Water balance, Water availability, Water demand, Code river, Thiessen polygon, FJ mock
EVALUASI STABILITAS DINDING PENAHAN TANAH TIPE KANTILEVER DI DESA NGROTO, KECAMATAN PUJON, KABUPATEN MALANG
Authors: Suhudi Suhudi , Ehok Simplisius
Published: April 2021

AbstractWavy topographical conditions with high rainfall intensity cause cantilever type retaining wall on Jalan Brigjen Abdul Manan Wijaya in Ngroto village, Pujon District, Malang Regency, which borders the Konto River avalanche. The stability of the retaining wall can be expressed as Fs (Savety Factor). Factor value the security that is reviewed is the Fs bolster, namely the safety factor against the overthrowing force, the Fs shear is the safety factor against the shear force at the base of the retaining wall, Fs, the bearing capacity of the soil is a factor safety of soil bearing capacity. The purpose of this evaluation is to determine the wall planning cantilever type retaining wall and evaluate the stability of cantilever type retaining wall against the dangers of rolling, shearing, soil bearing capacity and knowing the budget plan for wall planning Cantilever type retaining wall. The result of this evaluation shows the cantilever retaining wall with dimensions H = 7, B = 3.5 Ta = 0.5 Tb = 0.7 D = 1 declared safe with the safety value for normal water level fs slide 1.8> 1.5 (safe), fs roll 2> 1.5 (safe), fs ground bearing capacity 186.8> 4752.86 (safe). Water face flood fs shear 2,6> 1,5 (safe) fs rolling 2,3> 1,5 (safe) fs soil bearing capacity 186.8> 4752.86 (safe). The total cost required for the construction of a cantilever type retaining wall of length 20 m T = 7 width 3.5 m for Rp. 290,570,000.Keywords: Retaining walls, Dimensions, Stability of retaining walls
KUAT TEKAN BETON PADA BERBAGAI VARIASI UMUR UJI DENGAN BAHAN RETARDER TETES GULA/ MOLASSES
Authors: Riyanto Sugeng
Published: April 2021

Tetes gula atau Molasses merupakan hasil sampingan pada proses pembuatan gula dari tebu. Tetes gula ini berupa larutan kental berwarna hitam kecoklatan dan mempunyai sifat fisik yang mudah larut dalam air dingin dan kadar senyawa gula masih berkisar antara 50 – 60%. Secara umum, bahan additive bersifat retarder terbentuk dengan senyawa dasarnya gula, maka tetes gula pada kadar tertentu dapat digunakan sebagai retarder atau memperlambat proses hidrasi semen dalam beton. Penelitian ini bertujuan untuk mengetahui perubahan kenaikan kuat tekan beton pada berbagai variasi umur dengan bahan retarder tetes gula dibandingkan terhadap campuran beton normal. Kadar tetes gula dinyatakan dalam volume per berat semen dan dibuat bervariasi dari 0,00 sampai 1,50 cc dengan interval 0,25 cc per kg semen. Sedangkan umur pengujian diambil 1, 2, 3, 7, 14, 21, dan 28 hari. Bentuk benda uji yang dibuat  silinder Ø 15x30 cm, dengan masing-masing perlakuan diberikan perulangan 5 (lima) kali. Kuat tekan beton ditentukan melalui pengujian statis dengan menggunakan mesin uji tekan beton bertenaga listrik. Hasil pengujian diperoleh bahwa tetes gula dapat digunakan sebagai retarder dengan kadar optimum tetes gula rerata 0,81 cc per kg semen dan persentase kenaikan kuat tekan beton 49,06%Kata-kata kunci:  tetes gula/molasses, additive, retarder, kuat tekan beton
OPTIMALISASI CASHFLOW MENGGUNAKAN METODE PENJADWALAN EST DAN PENGATURAN SUMBERDAYA PADA PROYEK BANGUNAN GEDUNG
Authors: Riskijah Sitti Safiatus
Published: April 2021

An appropriate and accurate management of financial source will be able to run activities of a project well and increases the contractor’s profit. This reasearch aims at determining the kind of optimum cashflow of a multi purpose construction project in Malang. Schedule, debits and credits, loan interest, installment plan, completed with the system of contract payment from the owner to the contractor were needed to make the cash flow. It was done by employing 20% and 0% down payment based on EST (Earlierst Start Time), 27 kinds of resource payment system varied in start, prorate, and end of cost, material, and work. Each Cash flow will not only determine the balance of payments and total credits of each period but also the profit. The findings the show that the kinds of Cash flow which gives maximum profit for contractors, are as follow: 1) the one based on EST with no down payment system at a difference profit of IDR 109.708.207,51 or 1,5%; 2) the one based on arrangement of cost, material, and work payment system which results in Start-End-End payment; 3) the application of the two Cash flow systems results in  Start-End-End system is able to give maximum profit of IDR 7.869.632.694,74.Keywords: Cash flow, debit, credit, payment system, maximum profit
ANALISA FINANSIAL PROYEK BANGUNAN GEDUNG (STUDI KASUS: PROYEK GEDUNG INTENSIF RSSA MALANG)
Authors: Fauziah S.C.S. Maisarah, Suselo Utoyo Firda Eka Damayanti,
Published: April 2021

The 4,333 m2-four-floored Intensive Building development project was carried out to accommodate additional facility to the hospital due to the increasing number of patients. Financial analysis is necessary to find out the project cost and to see the operational cost sufficient to meet the building management for 20 years life span according to the building standard. The aims of this analysis are to find out the project cash flow during the life span, financial report, feasibility analysis, and sensitivity analysis. Some data of budgeting, technical drawings, medical equipment procurement cost, hospitalization and out-patient rates were needed. All of them were obtained from interviews and calculations. While Net Present Value (NPV), Internal Rate of Return (IRR), Benefit Cash Ratio (BCR), Pay Back Period (PP), and sensitivity analysis were employed to determine the financial feasibility. The calculations result in financial analysis of NPV = 32,989,940,121 > 0; BCR = 1.34 > 1; IRR = 18.83% > Minimum Attractive Rate of Return (MARR) = 10%; and PP = 7.2 years. The results of the sensitivity analysis show that the most influential factor is occupancy rate, but the project is feasible.Keywords: feasibility, financial analysis, intensive building.
PEMANFAATAN SILINDER LIMBAH TES BETON SEBAGAI DINDING PENAHAN TANAH TIPE GRAVITASI
Authors: Muhammad, Gerard Aponno, Suselo Utoyo Dimas Prasetyo
Published: April 2021

The utilization of concrete-test-cylindrical waste was few due to it’s tendency to roll over when being stacked and the stacked form was not uniform like cubed waste. That is why the writer wants to use the cylindrical waste as a material of gravity-typed retaining wall.The purpose of this study is to find out the stability, cost, and implemention method of cylindrical waste as a material such retaining wall.The stability analysis of retaining wall made from cylindrical concrete was compared to commonly stoned retaining wall through trial and error method. The next step was to make the construction of retaining wall made from cylindrical concrete and stone to see the implemetion method and cost needed per m3.       Stability analysis results in cylindrical concrete retaining wall safe from rolling, sliding, and reaction of foundation soil. Compared to stoned retaining wall of 3,00 m tall and 1,70 m long, it has safety factor (SF) Fgl = 2.13, Fgs = 2,37, and qumax = 4,07 ton/m2  which means it is close to the FS of stoned retaining wall Fgl = 2.18, Fgs = 2,39, and qumax = 9,89 ton/m2 ; at IDR 1.012.093,74 per m3 which means it is IDR 389.553 more expensive  ; and it is of horizontal arragement.Keywords: retaining wall, concrete-test cylinder, stability, cost estimate, horizontal arrangement.
ANALISA SUPPLY DAN DEMAND BETON READYMIX DI KOTA MALANG
Authors: Wardhana, Suhariyanto, Sugeng Riyanto Angga Saputra Dwi
Published: April 2021

As civil constructions are growing rapidly in Malang, readymix concrete is in a great demand. The writer intends to find out the capacity of average readymix supply of 4 different companies, the capacity of average readymix demand of some construction projects in Malang, and some influential problems of both readymix supply and demand. This thesis includes a qualitative descriptive study. Questionnaires were distributed to some users and producers of readymix concrete in Malang.The questionnaires result is average 117.5 m3/day capacity of readymix supply in normal production and average 200 m3/day capacity of readymix supply in peak production, average 92 m3/day capacity of readymix demand large scale users, average 45 m3/day capacity of readymix demand medium scale users, average 17 m3/day capacity of readymix demand small scale users, and some problems of less material to make readymix concrete and less concrete mixer truck unit to service users.Keywords: demand, producer, readymix concrete, supply, user
APLIKASI VALUE ENGINEERING PADA RUMAH TINGGAL TIPE 90/180, 135/180, DAN 223/253 DI PERUMAHAN BLIMBING PERMAI KOTA MALANG
Authors: Pradana, Sumardi, Udi Subagyo Haris Asta
Published: April 2021

The application of value engineering to Blimbing Permai Residence (BPR) aimed to sistematically organize and apply a technique that identifies the product to meet the required function at the lowest price. It was applied to houses of 90/180, 135/180, and 223/253 at BPR without lowering the price. Pareto and function analysis method were employed to analize some phases of work plan to result in some more objective alternatives based on several variables. Both methodes result in breakdown cost in a chronological order of the highest itemized work cost to the lowest one. The analyses result in some work items possibly to replace, they are of wall, roof, truss, and concrete slab works of 90/180 type; masonry, truss, and roff tiling of 135/180 type; concrete, wall and roofing of 225/253 type. The Value Engineering result in hebel bricks to replace conventional ones; ceramic concrete slab to replace conventional concrete one ; light galvanic to replace wooden truss ; granite tile to replace marble ones. Its a result type 90/180 is more economical at IDR.250,292,433.03 or 10.5 % of the existing IDR.276,591,438.78. The type 135/180 is more economical at IDR.346,840,945.04 or 11.07 % of the existing IDR.385,047,844.51. At last of type 223/253 is more economical at IDR.595,156,885.77 or 17.08 % of the existing IDR.667,232,563.47.Keywords: breakdown cost, function analysis, Pareto Analysis, value engineering
KARAKTERISTIK CAMPURAN AC-BASE DENGAN ASPAL PENETRASI 60/70 DAN PENETRASI 80/100
Authors: Erdiansa Andi
Published: April 2021

Asphalt Concrete Base adalah produk hasil pencampuran antara agregat kasar, agregat halus, filler, dan aspal keras pada suhu tertentu kemudian dihampar dan digilas pada suhu tertentu pula. Ciri khas dari campuran aspal AC-Base adalah penggunaan agregat bergradasi menerus.Disyaratkan dalam spesifikasi pekerjaan jalan diharuskan menggunakan aspal pen.60/70, salah satu hambatan yang  ditemukanadalah stock aspal pen. 60/70 dipasaran tidak ada terutama aspal import, penggunaa beralih pada aspal curah atau aspal pen.80/100.Penelitian ini mencoba menggunakan Aspal penetrasi 60/70 dan penetrasi 80/100, metode yang digunakan pada penelitian ini adalah Metode Marshall Test yang bertujuan membandingkan nilai karakteristik campuran AC-BaseHasil penelitian menunjukkan Karakteristik Campuran AC-Base untuk nilai stabilitas aspal pen.60/70 lebih tinggi sebaliknya nilai flow  aspal pen.80/100 lebih besar, hal ini sangat dipengaruhi tingkat penetrasi dan titik leleh aspal. Nilai VFB aspal pen.80/100 lebih tinggi pada kadar aspal sampai 6%, sebaliknya nilai VIM 60/70 lebih tinggi. Sedangkan untuk kadar aspal lebih besar 6%, nilai VFB dan VIM grafiknya cendrung nilai keduanya sama. Perbandingan nilai VMA aspal pen.60/70 lebih besar dibandingkan aspal pen.80/100 pada kondisi kadar aspal lebih kecil dari 6% hal disebabkan titik leleh aspal 60/70 lebih tinggi. Sedangkan untukkadar aspal lebih besar dari 6 % nilai VMA aspal pen. 80/100 lebih tinggiKata Kunci: Penetrasi, Marshall Test, Karakteritik AC-Base
PENERAPAN VALUE ENGINEERING PADA PROYEK PEMBANGUNAN KANTOR TANAMAN DAN TUK PG. KEBON AGUNG MALANG
Authors: Zettyara, Wahiddin, Agnes Hanna Patty Devi
Published: April 2021

Completed with the project price of IDR 10,750,900,000.00, the 4-floor office in the area of about 6,688 m2 is located on Jl. Raya Kebon Agung Malang. The existing beam was constructed using concrete beam. The objective of analysis is to make alternatives of beam work by employing Value Engineering (VE) analysis in order to find out the most efficient price. The three beam works to alternate the existing are (1) I section concrete beam, (2) T section concrete beam and (3) composite beam. The analysis started with a literature study in VE references, material cost, and beam work of the project. Next, the structure strength and cost of the existing beam was analyzed followed by the analyses of each alternatives. Finally, the structure strength and cost the existing beam and the alternatives were compared. The results of the study shows structurally the smaller sectional shape the smaller the value of øMn and Mu are produced. In term of cost, the alternative that has the greatest value of saving is alternative 2 or T-shaped concrete beam of 29.39%.Keywords: value engineering, cost saving, beam structure
OPTIMASI PENGGUNAAN ALAT BERAT PADA PROYEK JALAN TOL GEMPOL-PANDAAN STA 5+500 – STA 11+500
Authors: Chrisna Wijaya, Fadjar Purnomo, Adi Muljo Muhammad
Published: April 2021

Cut and fill is one of the jobs that have to be considered carefully because a lot of heavy equipment is employed. Due to its different capacity, heavy equipment must be carefully and properly selected to maximize its use and minimize the leasing cost. The objective of the study is to find out the optimal time used to operate each heavy equipment, and the leasing cost.  The data were of 5 km project span consisting of 1.425 km cut and 4.575 m3 fill, 1,661,104 m3 cut volume and 377,685.9 m3 fill volume. Excavator PC200-8, dump truck Hino FM260 JD, dozer D65PE-12, compactor SD160 were employed during 1,925 hours, total cost of this project IDR 255.125.700.000,00, and percentage of cut and fill cost is 13,496%.First, identifying the work type and work volume was done to determine the suitable heavy equipment used and the number. Second, determining the decision variable, objective function, and problem function, then put them into linear programming. Those data were processed through LINDO program to find out duration and the overall cost of heavy equipment. The analyses result in 4 alternatives. Alternative 2 is of combination of 21 excavators PC200-8, 55 dump truck Hino FM260 JD, 1 dozers D65PE-12, and 2 compactors SD160. 1.902,13 hours duration at IDR 31.369.910.000,00 (thirtysix billion two hundred and twelve million thirtyseven thousand Indonesian rupiah) is chosen or 7%more expensive than contractor price.Keywords: cut and fill, heavy equipment, duration and total cost
PERENCANAAN JEMBATAN RANGKA BAJA BENTANG 50 METER
Authors: Putri, Sudarmanto, Yunaefi Risky Amaliya
Published: April 2021

To facilitate the flow of transport from one region to the other region dan increase sectors of the economy the need for bridges as a means of connecting. Steel bridge is the one arranged from steel beam joined with gusset plate, binder keeling nails, bolts or welding. The purpose of the study is to design a 50 m-spam steel truss bridge of 10,4 m width. The design was based on Highway Bridge Loading Design, ASD and PPBBI 1984. The concrete strength is of  (fc ') 30 MPa and the steel strength of BJ 44. Designed manually with no pillar, the bottom only consists of abutment and foundation. The main framework was designed by employing equilibrium of gusset point dan reitter method was employed to found out the beam force and influential linesof the framework. The soil survey data were obtained throught Begemann Friction Cone (Bikonus) or Dutch Cone Mechanical type test. The soil is melatirely similar type of sandy clay mix and hard soil in the depth of 5 meters. The design result in the main framework using profile WF 400 x 400 x 20 x 35, longitudinal girder of WF 350 x 350 x 13 x 13 dan crossed girder of WF 800 x 300 x 16 x 30 The foundation  is of  pile foundation at IDR 5.543.070.300,00,- within 172 work days.Keywords: steel, truss, bridge
Weed flora in modern agrotechnical literature
Authors: Tikhonov Alexander
Published: April 2021

The results of the analysis of literature sources, directly and indirectly, reflecting the composition and structure of agro phytocoenoses and the role of the weed component in them are presented, generally showing the degree of knowledge of this issue. The dominant approaches to the perception of weed flora by domestic researchers and typical methods of interaction are shown.
L3 — a new innovative variety winter vetch for the Ural and Central Chernozem regions of Russia
Authors: Tyurin Yuri , Kostenko Sergey
Published: April 2021

Winter vetch, shaggy provides high-protein animal feed in the spring on complexes, food from this plant is perfectly absorbed by all domestic animals. The new variety of winter shaggy vetch "L3" surpasses the existing varieties in the productivity of green mass, dry matter, and seed productivity. In terms of protein content, this variety is not inferior to most varieties. The variety is recommended for two regions, but later zoning can be expanded. The variety is also characterized by high winter hardiness and drought resistance.
Efficiency of fertilizer application on seed stands of birdsfoot trefoil
Authors: Zolotarev Vladimir
Published: April 2021

On sod-podzolic medium-loamy soils of the Central Non-Chernozem region of Russia with an average availability of mobile forms of phosphorus and an average close to low potassium content, high efficiency of using potash fertilizer together with phosphorus on birdsfoot trefoil seed crops was established. Effective doses of phosphorus-potassium fertilizers, providing an increase in seed yield in the first year by 42–47% and, according to the aftereffect, in the second year by 17–33%, are the application of P30–60K90–120. Keywords: Birdsfoot trefoil (Lotus corniculatus L.), seed herbage, phosphoric and potash mineral fertilizers, yield, seeds, sowing qualities.
Hybrid of meadow fescue "VIK-5-34" for growing on high agrophones on meadows and pastures in the European part of Russia
Authors: Kostenko Sergey , Malyuzhenets Evgenia , Kostenko Natalia , Pampura Elena , Terekhova Nadezhda
Published: April 2021

Meadow fescue is one of the best grasses for forage production in most of Russia, being inferior in productivity to pasture ryegrass in the country's reserve; it is much superior to it in other regions in terms of longevity, sea resistance and drought resistance. This species is also less affected by fungal diseases, grows well in herb mixtures with both clover and alfalfa or with other legumes and cereals. The new variety "VIK-5-34" is intended for cultivation on high agricultural grounds in farms with a high level of agriculture. The variety can be used both for foraging and for creating pastures.
Rapid Evolution of Invasive Weeds Under Climate Change: Present Evidence and Future Research Needs
Authors: Clements David R. , Jones Vanessa L.
Published: April 2021

Although evolution has been often seen as a gradual process through a Darwinian lens, far more rapid evolutionary change has been observed in recent times. Recent examples documenting the potential speed of invasive plant evolution have included: latitudinal flowering clines, life history shifts, or abrupt changes in morphology. The timescales for such observations range from centuries down to <5 years. Invasive weeds provide good models for the rapid changes, partly because invasive weeds exhibit unique evolutionary mechanisms integral to their success. For example, purging of their genetic load may enable invasive plants to adapt more rapidly. Other genetic mechanisms include plasticity as an evolved trait, hybridization, polyploidy, epigenetics, and clonal division of labor. It is well-demonstrated that anthropogenic stressors such as habitat disturbance or herbicide use may work synergistically with climate change stressors in fostering rapid weed evolution. Changing temperatures, moisture regimes and extreme climate events operate universally, but invasive plant species are generally better equipped than native plants to adapt. Research on this potential for rapid evolution is critical to developing more proactive management approaches that anticipate new invasive plant ecotypes adapted to changing climatic conditions.
Integration of Proteomics and Metabolomics Into the Design, Build, Test, Learn Cycle to Improve 3-Hydroxypropionic Acid Production in Aspergillus pseudoterreus
Authors: Pomraning Kyle R. , Dai Ziyu , Munoz Nathalie , Kim Young-Mo , Gao Yuqian , Deng Shuang , Kim Joonhoon , Hofstad Beth A. , Swita Marie S. , Lemmon Teresa , Collett James R. , Panisko Ellen A. , Webb-Robertson Bobbie-Jo M. , Zucker Jeremy D. , Nicora Carrie D. , De Paoli Henrique , Baker Scott E. , Burnum-Johnson Kristin E. , Hillson Nathan J. , Magnuson Jon K.
Published: April 2021

Biological engineering of microorganisms to produce value-added chemicals is a promising route to sustainable manufacturing. However, overproduction of metabolic intermediates at high titer, rate, and yield from inexpensive substrates is challenging in non-model systems where limited information is available regarding metabolic flux and its control in production conditions. Integrated multi-omic analyses of engineered strains offers an in-depth look at metabolites and proteins directly involved in growth and production of target and non-target bioproducts. Here we applied multi-omic analyses to overproduction of the polymer precursor 3-hydroxypropionic acid (3HP) in the filamentous fungus Aspergillus pseudoterreus. A synthetic pathway consisting of aspartate decarboxylase, beta-alanine pyruvate transaminase, and 3HP dehydrogenase was designed and built for A. pseudoterreus. Strains with single- and multi-copy integration events were isolated and multi-omics analysis consisting of intracellular and extracellular metabolomics and targeted and global proteomics was used to interrogate the strains in shake-flask and bioreactor conditions. Production of a variety of co-products (organic acids and glycerol) and oxidative degradation of 3HP were identified as metabolic pathways competing with 3HP production. Intracellular accumulation of nitrogen as 2,4-diaminobutanoate was identified as an off-target nitrogen sink that may also limit flux through the engineered 3HP pathway. Elimination of the high-expression oxidative 3HP degradation pathway by deletion of a putative malonate semialdehyde dehydrogenase improved the yield of 3HP by 3.4 × after 10 days in shake-flask culture. This is the first report of 3HP production in a filamentous fungus amenable to industrial scale biomanufacturing of organic acids at high titer and low pH.
Functional Mapping of Adhesiveness on Live Cells Reveals How Guidance Phenotypes Can Emerge From Complex Spatiotemporal Integrin Regulation
Authors: Robert Philippe , Biarnes-Pelicot Martine , Garcia-Seyda Nicolas , Hatoum Petra , Touchard Dominique , Brustlein Sophie , Nicolas Philippe , Malissen Bernard , Valignat Marie-Pierre , Theodoly Olivier
Published: April 2021

Immune cells have the ubiquitous capability to migrate disregarding the adhesion properties of the environment, which requires a versatile adaptation of their adhesiveness mediated by integrins, a family of specialized adhesion proteins. Each subtype of integrins has several ligands and several affinity states controlled by internal and external stimuli. However, probing cell adhesion properties on live cells without perturbing cell motility is highly challenging, especiallyin vivo. Here, we developed a novelin vitromethod using micron-size beads pulled by flow to functionally probe the local surface adhesiveness of live and motile cells. This method allowed a functional mapping of the adhesiveness mediated by VLA-4 and LFA-1 integrins on the trailing and leading edges of live human T lymphocytes. We show that cell polarization processes enhance integrin-mediated adhesiveness toward cell rear for VLA-4 and cell front for LFA-1. Furthermore, an inhibiting crosstalk of LFA-1 toward VLA-4 and an activating crosstalk of VLA-4 toward LFA-1 were found to modulate cell adhesiveness with a long-distance effect across the cell. These combined signaling processes directly support the bistable model that explains the emergence of the versatile guidance of lymphocyte under flow. Molecularly, Sharpin, an LFA-1 inhibitor in lymphocyte uropod, was found involved in the LFA-1 deadhesion of lymphocytes; however, both Sharpin and Myosin inhibition had a rather modest impact on adhesiveness. Quantitative 3D immunostaining identified high-affinity LFA-1 and VLA-4 densities at around 50 and 100 molecules/μm2in basal adherent zones, respectively. Interestingly, a latent adhesiveness of dorsal zones was not grasped by immunostaining but assessed by direct functional assays with beads. The combination of live functional assays, molecular imaging, and genome editing is instrumental to characterizing the spatiotemporal regulation of integrin-mediated adhesiveness at molecular and cell scales, which opens a new perspective to decipher sophisticated phenotypes of motility and guidance.
Antibacterial Composite Materials Based on the Combination of Polyhydroxyalkanoates With Selenium and Strontium Co-substituted Hydroxyapatite for Bone Regeneration
Authors: Marcello Elena , Maqbool Muhammad , Nigmatullin Rinat , Cresswell Mark , Jackson Philip R. , Basnett Pooja , Knowles Jonathan C. , Boccaccini Aldo R. , Roy Ipsita
Published: April 2021

Due to the threat posed by the rapid growth in the resistance of microbial species to antibiotics, there is an urgent need to develop novel materials for biomedical applications capable of providing antibacterial properties without the use of such drugs. Bone healing represents one of the applications with the highest risk of postoperative infections, with potential serious complications in case of bacterial contaminations. Therefore, tissue engineering approaches aiming at the regeneration of bone tissue should be based on the use of materials possessing antibacterial properties alongside with biological and functional characteristics. In this study, we investigated the combination of polyhydroxyalkanoates (PHAs) with a novel antimicrobial hydroxyapatite (HA) containing selenium and strontium. Strontium was chosen for its well-known osteoinductive properties, while selenium is an emerging element investigated for its multi-functional activity as an antimicrobial and anticancer agent. Successful incorporation of such ions in the HA structure was obtained. Antibacterial activity against Staphylococcus aureus 6538P and Escherichia coli 8739 was confirmed for co-substituted HA in the powder form. Polymer-matrix composites based on two types of PHAs, P(3HB) and P(3HO-co-3HD-co-3HDD), were prepared by the incorporation of the developed antibacterial HA. An in-depth characterization of the composite materials was conducted to evaluate the effect of the filler on the physicochemical, thermal, and mechanical properties of the films. In vitro antibacterial testing showed that the composite samples induce a high reduction of the number of S. aureus 6538P and E. coli 8739 bacterial cells cultured on the surface of the materials. The films are also capable of releasing active ions which inhibited the growth of both Gram-positive and Gram-negative bacteria.
An Integrated Enzymatic Approach to Produce Pentyl Xylosides and Glucose/Xylose Laurate Esters From Wheat Bran
Authors: Jocquel Chloé , Muzard Murielle , Plantier-Royon Richard , Rémond Caroline
Published: April 2021

Alkyl glycosides and sugars esters are non-ionic surfactants of interest for various applications (cosmetics, food, detergency,…). In the present study, xylans and cellulose from wheat bran were enzymatically converted into pentyl xylosides and glucose and xylose laurate monoesters. Transglycosylation reaction catalyzed by the commercial enzymatic cocktail Cellic Ctec2 in the presence of pentanol led to the synthesis of pentyl β-D-xylosides from DP1 to 3 with an overall yield of 520 mg/g of xylans present in wheat bran. Enzymatic hydrolysis of wheat bran with Cellic Ctec2 and subsequent acylation of the recovered D-glucose and D-xylose catalyzed by the commercial lipase N435 in the presence of lauric acid or methyl laurate produced one D-glucose laurate monoester and one D-xylose laurate monoester. An integrated approach combining transglycosylation and (trans)esterification reactions was successfully developed to produce both pentyl xylosides and D-glucose and D-xylose laurate esters from the same batch of wheat bran.
Gene Transcript Alterations in the Spinal Cord, Anterior Cingulate Cortex, and Amygdala in Mice Following Peripheral Nerve Injury
Authors: Su Songxue , Li Mengqi , Wu Di , Cao Jing , Ren Xiuhua , Tao Yuan-Xiang , Zang Weidong
Published: April 2021

Chronic neuropathic pain caused by nerve damage is a most common clinical symptom, often accompanied by anxiety- and depression-like symptoms. Current treatments are very limited at least in part due to incompletely understanding mechanisms underlying this disorder. Changes in gene expression in the dorsal root ganglion (DRG) have been acknowledged to implicate in neuropathic pain genesis, but how peripheral nerve injury alters the gene expression in other pain-associated regions remains elusive. The present study carried out strand-specific next-generation RNA sequencing with a higher sequencing depth and observed the changes in whole transcriptomes in the spinal cord (SC), anterior cingulate cortex (ACC), and amygdala (AMY) following unilateral fourth lumbar spinal nerve ligation (SNL). In addition to providing novel transcriptome profiles of long non-coding RNAs (lncRNAs) and mRNAs, we identified pain- and emotion-related differentially expressed genes (DEGs) and revealed that numbers of these DEGs displayed a high correlation to neuroinflammation and apoptosis. Consistently, functional analyses showed that the most significant enriched biological processes of the upregulated mRNAs were involved in the immune system process, apoptotic process, defense response, inflammation response, and sensory perception of pain across three regions. Moreover, the comparisons of pain-, anxiety-, and depression-related DEGs among three regions present a particular molecular map among the spinal cord and supraspinal structures and indicate the region-dependent and region-independent alterations of gene expression after nerve injury. Our study provides a resource for gene transcript expression patterns in three distinct pain-related regions after peripheral nerve injury. Our findings suggest that neuroinflammation and apoptosis are important pathogenic mechanisms underlying neuropathic pain and that some DEGs might be promising therapeutic targets.
Advanced Biomedical Applications of Reactive Oxygen Species-Based Nanomaterials in Lung Cancer
Authors: Zhao Nan , Xin Hua , Zhang Lening
Published: April 2021

Over the years, lung cancer remains the leading cause of cancer deaths in worldwide. In view of this, increasingly importance has been attached to the further optimization and improvement of its treatment. Reactive oxygen species (ROS) play a key role in regulating tumor development and anti-cancer treatment. Recently, the development of nanomaterials provides new platforms for ROS-based cancer treatment methods, which can help to reduce side effects and enhance anti-cancer effects. In recent years, a variety of lung cancer treatment models have been reported, such as chemodynamic therapy (CDT), photodynamic therapy (PDT), radiation therapy (RT) and controlled drug release (CDR). In this review, we are going to discuss the possible mechanism of action and current research status of ROS-based nanomaterials in the treatment of lung cancer in order to provide constructive ideas for relative research and expect this work could inspire the future development of novel lung cancer treatments.
Molecular Epidemiology of Hypervirulent Carbapenemase-Producing Klebsiella pneumoniae
Authors: Hu Dakang , Li Yuming , Ren Ping , Tian Dongxing , Chen Wenjie , Fu Pan , Wang Weiwen , Li Xiaobin , Jiang Xiaofei
Published: April 2021

Objective

To investigate the overall distributions of key virulence genes in Klebsiella pneumoniae, especially the hypervirulent blaKPC-positive K. pneumoniae (Hv-blaKPC(+)-KP).

Methods

A total of 521 complete genomes of K. pneumoniae from GenBank were collected and analyzed. Multilocus sequence typing, molecular serotyping, antibiotic-resistance, virulence genes and plasmid replicon typing were investigated.

Results

Positive rates of virulence genes highly varied, ranging from 2.9 (c-rmpA/A2) to 99.6% (entB). Totally 207 strains presented positive fimH, mrkD, entB and wzi and 190 showed positive fimH, mrkD, entB, irp2 and wzi, which were the two primary modes. A total of 94, 165 and 29 strains were denoted as hypervirulent K. pneumoniae (HvKP), blaKPC(+)-KP and Hv-blaKPC(+)-KP. ST11 accounted for 17 among the 29 Hv-blaKPC(+)-KP strains; Genes iucA, p-rmpA2 and p-rmpA were positive in 28, 26 and 18 Hv-blaKPC(+)-KP strains respectively. Among the 29 Hv-blaKPC(+)-KP strains exhibiting four super clusters from GenBank, IncHI1B plasmids carrying virulence genes and IncFII ones with blaKPC were responsible for both 23 strains respectively.

Conclusions

Positive rates of virulence genes vary remarkably in K. pneumoniae. Genes iucA, p-rmpA2 and p-rmpA were primary ones inducing Hv-blaKPC(+)-KP. IncHI1B plasmids carrying virulence genes and IncFII ones with blaKPC constitute the primary combination responsible for Hv-blaKPC(+)-KP. The making of Hv-blaKPC(+)-KP is mostly via blaKPC(+)-KP acquiring another plasmid harboring virulence genes.
Histology and Geochemistry of Allosaurus (Dinosauria: Theropoda) From the Cleveland-Lloyd Dinosaur Quarry (Late Jurassic, Utah): Paleobiological Implications
Authors: Ferrante Christophe , Cavin Lionel , Vennemann Torsten , Martini Rossana
Published: April 2021

The Late JurassicAllosaurusis one of the better-studied dinosaurs. A histological and geochemical study of a tibia and a femur ofA. fragilisrecovered in the Upper Jurassic Cleveland-Lloyd Dinosaur Quarry, Utah, United States has been done in order to address growth characteristics of this species. The two bones, probably belonging to separate individuals, are among the largest known for this species, which make them suitable to address such issues. The inclusion of our data on femur growth markings in the previously published data reflects a range of growth variability rather than two distinct growth strategies. The tibia has a well-developed external fundamental system indicating somatic maturity achievement. Using a quantitative method of superimposition to retrocalculate missing lines of arrested growth, the tibia appears to correspond to an individual that reached its skeletal maturity at 22 years and died at approximately 26 years. In the tibia, the concentration of zinc, a potential biomarker associated with bone formation, displays a higher concentration in zones of rapid growth compared to annuli. There is no direct relationship between the values of δ18Opand the lines of arrested growth distribution. The absence of relations between the histological organization and an enrichment in REE of the bone, indicates that the variations of δ18Oplikely represent a diagenetic process rather than a primordial, biologic composition. However, the geochemical composition of the bones is not homogeneous along the sections, indicating that the signal variations have not been completely erased by diagenesis.
Contribution of Particulate and Mineral-Associated Organic Matter to Potential Denitrification of Agricultural Soils
Authors: Surey Ronny , Kaiser Klaus , Schimpf Corinna M. , Mueller Carsten W. , Böttcher Jürgen , Mikutta Robert
Published: April 2021

Water-extractable organic carbon (WEOC) is considered as the most important carbon (C) source for denitrifying organisms, but the contribution of individual organic matter (OM) fractions (i.e., particulate (POM) and mineral-associated (MOM)) to its release and, thus, to denitrification remains unresolved. Here we tested short-time effects of POM and MOM on potential denitrification and estimated the contribution of POM- and MOM-derived WEOC to denitrification and CO2 production of three agricultural topsoils. Suspensions of bulk soils with and without addition of soil-derived POM or MOM were incubated for 24 h under anoxic conditions. Acetylene inhibition was used to determine the potential denitrification and respective product ratio at constant nitrate supply. Normalized to added OC, effects of POM on CO2 production, total denitrification, and its product ratios were much stronger than those of MOM. While the addition of OM generally increased the (N2O + N2)-N/CO2-C ratio, the N2O/(N2O + N2) ratio changed differently depending on the soil. Gas emissions and the respective shares of initial WEOC were then used to estimate the contribution of POM and MOM-derived WEOC to total CO2, N2O, and N2O + N2 production. Water-extractable OC derived from POM accounted for 53–85% of total denitrification and WEOC released from MOM accounted for 15–47%. Total gas emissions from bulk soils were partly over- or underestimated, mainly due to nonproportional responses of denitrification to the addition of individual OM fractions. Our findings show that MOM plays a role in providing organic substrates during denitrification but is generally less dominant than POM. We conclude that the denitrification potential of soils is not predictable based on the C distribution over POM and MOM alone. Instead, the source strength of POM and MOM for WEOC plus the WEOC’s quality turned out as the most decisive determinants of potential denitrification.
Involvement of Interleukin-1 Receptor-Associated Kinase 4 and Interferon Regulatory Factor 5 in the Immunopathogenesis of SARS-CoV-2 Infection: Implications for the Treatment of COVID-19
Authors: Stoy Nicholas
Published: April 2021

Interleukin-1 receptor-associated kinase 4 (IRAK4) and interferon regulatory factor 5 (IRF5) lie sequentially on a signaling pathway activated by ligands of the IL-1 receptor and/or multiple TLRs located either on plasma or endosomal membranes. Activated IRF5, in conjunction with other synergistic transcription factors, notably NF-κB, is crucially required for the production of proinflammatory cytokines in the innate immune response to microbial infection. The IRAK4-IRF5 axis could therefore have a major role in the induction of the signature cytokines and chemokines of the hyperinflammatory state associated with severe morbidity and mortality in COVID-19. Here a case is made for considering IRAK4 or IRF5 inhibitors as potential therapies for the “cytokine storm” of COVID-19.
Case Report: Interferon-γ Restores Monocytic Human Leukocyte Antigen Receptor (mHLA-DR) in Severe COVID-19 With Acquired Immunosuppression Syndrome
Authors: Dickel Steffen , Grimm Clemens , Amschler Katharina , Schnitzler Sebastian Uwe , Schanz Julie , Moerer Onnen , Payen Didier , Tampe Bjoern , Winkler Martin Sebastian
Published: April 2021

Background

The major histocompatibility complex (MHC) class II characterized by monocytes CD14+ expression of human leukocyte antigen receptors (HLA-DR), is essential for the synapse between innate and adaptive immune response in infectious disease. Its reduced expression is associated with a high risk of secondary infections in septic patients and can be safely corrected by Interferon-y (IFNy) injection. Coronavirus disease (COVID-19) induces an alteration of Interferon (IFN) genes expression potentially responsible for the observed low HLA-DR expression in circulating monocytes (mHLA-DR).

Methods

We report a case of one-time INFy injection (100 mcg s.c.) in a superinfected 61-year-old man with COVID-19–associated acute respiratory distress syndrome (ARDS), with monitoring of mHLA-DR expression and clinical tolerance.

Observations

Low mHLA-DR pretreatment expression (26.7%) was observed. IFNy therapy leading to a rapid increase in mHLA-DR expression (83.1%).

Conclusions

Severe ARDS in a COVID-19 patient has a deep reduction in mHLA-DR expression concomitantly with secondary infections. The unique IFNy injection was safe and led to a sharp increase in the expression of mHLA-DR. Based on immune and infection monitoring, more cases of severe COVID-19 patients with low mHLA-DR should be treated by IFNy to test the clinical effectiveness.
Omega-3 Polyunsaturated Fatty Acid Intervention Against Established Autoimmunity in a Murine Model of Toxicant-Triggered Lupus
Authors: Pestka James J. , Akbari Peyman , Wierenga Kathryn A. , Bates Melissa A. , Gilley Kristen. N. , Wagner James G. , Lewandowski Ryan P. , Rajasinghe Lichchavi D. , Chauhan Preeti S. , Lock Adam L. , Li Quan-Zhen , Harkema Jack R.
Published: April 2021

Workplace exposure to respirable crystalline silica dust (cSiO2) has been etiologically linked to the development of lupus and other human autoimmune diseases. Lupus triggering can be recapitulated in female NZBWF1 mice by four weekly intranasal instillations with 1 mg cSiO2.This elicits inflammatory/autoimmune gene expression and ectopic lymphoid structure (ELS) development in the lung within 1 week, ultimately driving early onset of systemic autoimmunity and glomerulonephritis. Intriguingly, dietary supplementation with docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid (PUFA) found in fish oil, beginning 2 week prior to cSiO2challenge, prevented inflammation and autoimmune flaring in this novel model. However, it is not yet known how ω-3 PUFA intervention influences established autoimmunity in this murine model of toxicant-triggered lupus. Here we tested the hypothesis that DHA intervention after cSiO2-initiated intrapulmonary autoimmunity will suppress lupus progression in the NZBWF1 mouse. Six-week old NZWBF1 female mice were fed purified isocaloric diet for 2 weeks and then intranasally instilled with 1 mg cSiO2or saline vehicle weekly for 4 consecutive weeks. One week after the final instillation, which marks onset of ELS formation, mice were fed diets supplemented with 0, 4, or 10 g/kg DHA. One cohort of mice (n= 8/group) was terminated 13 weeks after the last cSiO2instillation and assessed for autoimmune hallmarks. A second cohort of mice (n= 8/group) remained on experimental diets and was monitored for proteinuria and moribund criteria to ascertain progression of glomerulonephritis and survival, respectively. DHA consumption dose-dependently increased ω-3 PUFA content in the plasma, lung, and kidney at the expense of the ω-6 PUFA arachidonic acid. Dietary intervention with high but not low DHA after cSiO2treatment suppressed or delayed: (i) recruitment of T cells and B cells to the lung, (ii) development of pulmonary ELS, (iii) elevation of a wide spectrum of plasma autoantibodies associated with lupus and other autoimmune diseases, (iv) initiation and progression of glomerulonephritis, and (v) onset of the moribund state. Taken together, these preclinical findings suggest that DHA supplementation at a human caloric equivalent of 5 g/d was an effective therapeutic regimen for slowing progression of established autoimmunity triggered by the environmental toxicant cSiO2.
Vitamin D Resistance as a Possible Cause of Autoimmune Diseases: A Hypothesis Confirmed by a Therapeutic High-Dose Vitamin D Protocol
Authors: Lemke Dirk , Klement Rainer Johannes , Schweiger Felix , Schweiger Beatrix , Spitz Jörg
Published: April 2021

Vitamin D3 (cholecalciferol) is a secosteroid and prohormone which is metabolized in various tissues to the biologically most active vitamin D hormone 1,25(OH)2D3 (calcitriol). 1,25(OH)2D3 has multiple pleiotropic effects, particularly within the immune system, and is increasingly utilized not only within prophylaxis, but also within therapy of various diseases. In this context, the latest research has revealed clinical benefits of high dose vitamin D3 therapy in autoimmune diseases. The necessity of high doses of vitamin D3 for treatment success can be explained by the concept of an acquired form of vitamin D resistance. Its etiology is based on the one hand on polymorphisms within genes affecting the vitamin D system, causing susceptibility towards developing low vitamin D responsiveness and autoimmune diseases; on the other hand it is based on a blockade of vitamin D receptor signaling, e.g. through pathogen infections. In this paper, we review observational and mechanistic evidence for the acquired vitamin D resistance hypothesis. We particularly focus on its clinical confirmation from our experience of treating multiple sclerosis patients with the so-called Coimbra protocol, in which daily doses up to 1000 I.U. vitamin D3 per kg body weight can be administered safely. Parathyroid hormone levels in serum thereby provide the key information for finding the right dose. We argue that acquired vitamin D resistance provides a plausible pathomechanism for the development of autoimmune diseases, which could be treated using high-dose vitamin D3 therapy.