Ultra scale-down approaches to enhance the creation of bioprocesses at scale: impacts of process shear stress and early recovery stages

The sensitivity of biological materials to shear stress conditions encountered during large-scale bioprocessing makes successful scale up from the bench challenging. Ultra scale-down technologies seek to use just millilitre quantities to enhance our understanding of the impact of the process environment as a basis for process optimisation. They can help speed translation of new biological discoveries to market and reduce risks encountered in scale up. They are important both as process discovery tools and as preparative tools to yield material for study of subsequent stages. In this review the focus is on the early recovery stages post fermentation or cell culture and in particular the use of continuous-flow and dead-end centrifugation integrated with preparative stages (e.g. flocculation) and subsequent depth filtration. Examples range from therapeutic antibodies, to rationally engineered (synthetic biology) host strains, to stem cells for therapy

Studying advanced mathematics in England: findings from a survey of student choices and attitudes

The UK Government has set a goal that the ‘vast majority’ of students in England will be studying mathematics to 18 by the end of the decade. The policy levers for achieving this goal include new Core Maths qualifications, designed for over 200,000 students who have achieved good grades at the age of 16 but then opt out of advanced or A-level mathematics. This paper reports findings from a cluster-sampled survey of over ten thousand 17-year-olds in England in 2015. Participants’ views on post-16 mathematics are presented and discussed. The main finding is that they are strongly opposed to the idea of compulsory mathematical study, but are less antithetical to being encouraged to study mathematics beyond 16. We consider how attitudes vary by gender, prior attainment, study patterns and future aspirations. The paper considers the implications of these findings in the current policy landscape

Lentiviral Vector Bioprocessing

Lentiviral vectors (LVs) are potent tools for the delivery of genes of interest into mammalian cells and are now commonly utilised within the growing field of cell and gene therapy for the treatment of monogenic diseases and adoptive therapies such as chimeric antigen T-cell (CAR-T) therapy. This is a comprehensive review of the individual bioprocess operations employed in LV production. We highlight the role of envelope proteins in vector design as well as their impact on the bioprocessing of lentiviral vectors. An overview of the current state of these operations provides opportunities for bioprocess discovery and improvement with emphasis on the considerations for optimal and scalable processing of LV during development and clinical production. Upstream culture for LV generation is described with comparisons on the different transfection methods and various bioreactors for suspension and adherent producer cell cultivation. The purification of LV is examined, evaluating different sequences of downstream process operations for both small- and large-scale production requirements. For scalable operations, a key focus is the development in chromatographic purification in addition to an in-depth examination of the application of tangential flow filtration. A summary of vector quantification and characterisation assays is also presented. Finally, the assessment of the whole bioprocess for LV production is discussed to benefit from the broader understanding of potential interactions of the different process options. This review is aimed to assist in the achievement of high quality, high concentration lentiviral vectors from robust and scalable processes

Laser Cooling of Optically Trapped Molecules

Calcium monofluoride (CaF) molecules are loaded into an optical dipole trap (ODT) and subsequently laser cooled within the trap. Starting with magneto-optical trapping, we sub-Doppler cool CaF and then load $150(30)$ CaF molecules into an ODT. Enhanced loading by a factor of five is obtained when sub-Doppler cooling light and trapping light are on simultaneously. For trapped molecules, we directly observe efficient sub-Doppler cooling to a temperature of $60(5)$ $\mu\text{K}$. The trapped molecular density of $8(2)\times10^7$ cm$^{-3}$ is an order of magnitude greater than in the initial sub-Doppler cooled sample. The trap lifetime of 750(40) ms is dominated by background gas collisions.Comment: 5 pages, 5 figure

Planta de producció d'àcid fòrmic

L'objectiu d'aquest treball és el disseny d'una planta de producció de 75.000 tones d'àcid fòrmic amb una puresa del 90%. El procés de producció consta de dues reaccions: la carbonilació del metanol i la hidròlisi del formiat de metil. Per dur a terme el procés, es necessiten un seguit d'equips com són reactors, columnes de destil·lació i d'absorció entre altres. Un cop dissenyats aquests equips, s'ha procedit a realitzar el seu control. El treball també contempla aspectes econòmics, de seguretat i mediambientals. Després de dur a terme els balanços necessaris, s'arriba a la conclusió de que la planta té una viabilitat limitada marcada per l'interès del mercat

Order of Magnitude Smaller Limit on the Electric Dipole Moment of the Electron

The Standard Model of particle physics is known to be incomplete. Extensions to the Standard Model, such as weak-scale supersymmetry, posit the existence of new particles and interactions that are asymmetric under time reversal (T) and nearly always predict a small yet potentially measurable electron electric dipole moment (EDM), d_e, in the range of 10^(−27) to 10^(−30) e·cm. The EDM is an asymmetric charge distribution along the electron spin (S) that is also asymmetric under T. Using the polar molecule thorium monoxide, we measured d_e = (–2.1±3.7_(stat)±2.5_(syst)) × 10−29 e·cm. This corresponds to an upper limit of ❘d_e❘ < 8.7 × 10^(−29) e·cm with 90% confidence, an order of magnitude improvement in sensitivity relative to the previous best limit. Our result constrains T-violating physics at the TeV energy scale

Equilibrium configurations of two charged masses in General Relativity

An asymptotically flat static solution of Einstein-Maxwell equations which describes the field of two non-extreme Reissner - Nordstr\"om sources in equilibrium is presented. It is expressed in terms of physical parameters of the sources (their masses, charges and separating distance). Very simple analytical forms were found for the solution as well as for the equilibrium condition which guarantees the absence of any struts on the symmetry axis. This condition shows that the equilibrium is not possible for two black holes or for two naked singularities. However, in the case when one of the sources is a black hole and another one is a naked singularity, the equilibrium is possible at some distance separating the sources. It is interesting that for appropriately chosen parameters even a Schwarzschild black hole together with a naked singularity can be "suspended" freely in the superposition of their fields.Comment: 4 pages; accepted for publication in Phys. Rev.

Probing exotic phenomena at the interface of nuclear and particle physics with the electric dipole moments of diamagnetic atoms: A unique window to hadronic and semi-leptonic CP violation

The current status of electric dipole moments of diamagnetic atoms which involves the synergy between atomic experiments and three different theoretical areas -- particle, nuclear and atomic is reviewed. Various models of particle physics that predict CP violation, which is necessary for the existence of such electric dipole moments, are presented. These include the standard model of particle physics and various extensions of it. Effective hadron level combined charge conjugation (C) and parity (P) symmetry violating interactions are derived taking into consideration different ways in which a nucleon interacts with other nucleons as well as with electrons. Nuclear structure calculations of the CP-odd nuclear Schiff moment are discussed using the shell model and other theoretical approaches. Results of the calculations of atomic electric dipole moments due to the interaction of the nuclear Schiff moment with the electrons and the P and time-reversal (T) symmetry violating tensor-pseudotensor electron-nucleus are elucidated using different relativistic many-body theories. The principles of the measurement of the electric dipole moments of diamagnetic atoms are outlined. Upper limits for the nuclear Schiff moment and tensor-pseudotensor coupling constant are obtained combining the results of atomic experiments and relativistic many-body theories. The coefficients for the different sources of CP violation have been estimated at the elementary particle level for all the diamagnetic atoms of current experimental interest and their implications for physics beyond the standard model is discussed. Possible improvements of the current results of the measurements as well as quantum chromodynamics, nuclear and atomic calculations are suggested.Comment: 46 pages, 19 tables and 16 figures. A review article accepted for EPJ

Corak Mazhab Pada Fatwa Dewan Syariah Nasional Majelis Ulama Indonesia (Dsn-Mui)

Penelitian ini menjelaskan mengenai corak mazhab pada fatwa Dewan Syari’ah Nasional MUI terkait tentang Musyarakah, Mudharabah dan Murabahah. Tiga hal yang menjadi fokus utama dalam penelitian ini yakni; 1) kedudukan Mazhab dan Fatwa di Indonesia; 2) eksistensi Dewan Syariah Nasional Majelis Ulama Indonesia, dan; 3) Corak mazhab pada fatwa Dewan Syariah Nasional Majelis Ulama Indonesia mengenai musyarakah, mudharabah dan murabahah. Penelitian ini bertujuan untuk mengetahui corak/tipe mazhab pada fatwa DSN-MUI terkait fatwa mengenai musyarakah, mudharabah dan murabahah. Metode Penelitian yang digunakan oleh penulis dalam penelitian ini adalah menggunakan metode penelitian hukum normatif yaitu metode penelitian hukum terhadap aturan hukum yang tertulis, dimana Fatwa DSN-MUI yang menjadi sumber sekaligus objek penelitian dan sumber data primer dalam penelitian yang dilakukan dan kemudian dianalisis oleh penulis. Berdasakan hasil penelitian maka diperoleh suatu kesimpulan bahwa dalam fatwa DSN-MUI terkait musyarakah, mudharabah dan murabahah, terdapat corak mazhab yang berbeda antar satu sama lain. Pada fatwa DSN-MUI mengenai Musyarakah, jika ditelaah secara substansi, ternyata cenderung bermazhab Hanafi, baik dari segi materi muatan fatwanya maupun secara aplikatif. Lain halnya dengan fatwa DSN-MUI mengenai Mudharabah, fatwa DSN-MUI tersebut lebih banyak mengambil dan menyepakati dasar-dasar hukum yang berasal dari mazhab Syafi’i sebagai fatwanya. Sedangkan fatwa DSN-MUI mengenai Murabahah, dasar hukum dan penetapan substansi dari materi fatwanya, lebih bersandarkan pada proporsi yang sama dari ke empat mazhab yang dikenal selama ini. Dengan demikian, Majelis Ulama Indonesia dalam mengeluarkan fatwa DSN untuk dilaksanakan di Indonesia, selalu mengacu dan berlandaskan dengan mazhab. Meski ada beberapa ketentuan-ketentuan yang disesuaikan dengan kondisi masa dan zaman, tetap tidak menyalahi kaidah-kaidah umum yang telah disampaikan oleh mazhab-mazhab terdahulu