Talking to the Infant in Psychoanalytic Parent-Infant Psychotherapy: An exploration of therapy process

This study examines how the aims and principles of psychoanalytic parent-infant psychotherapy (PPIP) are translated into the words used by the therapist to address the infant in the specific modality of parent-infant psychotherapy treatment (PIP) developed at the Anna Freud Centre. Literature Review. The literature review appraises different modalities of PPIP. It looks at the similarities in their theoretical and treatment frameworks and shows how the way in which the infant is understood in these different frameworks produces a differences in theory and technique. Empirical Paper. The empirical study is a naturalistic observational study of the therapist’s talk when in direct communication with the infant. The aim is to deepen our understanding of the what the therapist actually says and does in a therapy session. The results show that the therapist talks for a significant amount of time directly to the baby, and on a specific number of themes. Even though this is small single case study the findings contribute to our understanding of what therapists do in therapy. Reflective Commentary. The reflective commentary considers the process of engaging with doctoral research around a pre-verbal infant in treatment. It reflects on the personal experience of doing the research and considers how this experience has contributed to my development as a researcher and a child and adolescent psychotherapist

Numerical modelling of waves in the solar atmosphere

The Sun is the closest star to Earth and the bringer of life for all of us. Remove the Sun and Earth is rendered a lifeless, icy rock floating in outer space. It stands to reason that a thorough understanding of the workings of the Sun would be high priority in the scientific world, and beyond. The outer-most layer of the interior of the Sun comprises of what is known as the convection zone. This chaotic zone produces innumerable pressure waves, which propagate through the Sun. These waves carry the energy of the Sun to its atmosphere and beyond, and are thought to be responsible for the infamous ‘coronal heating problem’. The magnetic nature of the Sun allows both acoustic and magnetic waves, or various combinations of the two, to exist. This is where the complexity lies, with so many different types of waves being produced and exchanging energy between themselves, it is extremely difficult to pinpoint which waves are responsible for the observations we make. Observations and mathematical/physical theories of ever improving quality are used to understand the details of waves in the Sun, however they often lack a bridge to connect them, which is where numerical simulations come in. The work presented here provides a combination of 1.5, 2.5 and 3 dimensional simulations looking to explain how a variety of waves propagate and carry energy through the internal and external layers of the Sun. When a wave reaches a layer in the Sun’s atmosphere where the sound and Alfvén speeds coincide, it splits into two ‘modes’, a fast and slow mode. Recent mathematical findings suggested an incoming shock wave would not only split into its fast and slow components, but that both wave modes would be smoothed as they exit this area. Numerical simulations herein show that only the slow wave is smoothed, with the fast wave propagating unhindered. Within the Sun’s atmosphere, various steep gradients of its physical components are found. These gradients have been proposed to act as barriers to incoming waves, which can be partially reflected off them. Multiple reflection sites suggests cavities can be created that acoustic waves can resonate within. Numerical simulations herein show a stark increase in the velocity of frequencies proposed to be characteristic of a cavity within the chromosphere. This suggests cavities can exist within the Sun’s atmosphere and the amplitude of velocity observations from within these areas must be partially attributed to the resonant effects of the cavities themselves. Following the onset of some solar flares, ripples are observed on the Solar surface emanating from the flare site. These ripples show strong anisotropies in their appearance, a characteristic not well studied. Numerical simulations herein show that these anisotropies can be attributed to both the strength and inclination of the magnetic field but even more so by the nature of the impacting source. A source with motion perpendicular to the solar surface causes constructive interference and higher amplitude ripples are created along the axis of motion

The importance of Poly(ADP-Ribose) Polymerase as a sensor of unligated Okazaki fragments during DNA replication

Poly(ADP-ribose) is synthesized by PARP enzymes during the repair of stochastic DNA breaks. Surprisingly, however, we show that most if not all endogenous poly(ADP-ribose) is detected in normal S phase cells at sites of DNA replication. This S phase poly(ADP-ribose) does not result from damaged or misincorporated nucleotides or from DNA replication stress. Rather, perturbation of the DNA replication proteins LIG1 or FEN1 increases S phase poly(ADP-ribose) more than 10-fold, implicating unligated Okazaki fragments as the source of S phase PARP activity. Indeed, S phase PARP activity is ablated by suppressing Okazaki fragment formation with emetine, a DNA replication inhibitor that selectively inhibits lagging strand synthesis. Importantly, PARP activation during DNA replication recruits the single-strand break repair protein XRCC1, and human cells lacking PARP activity and/or XRCC1 are hypersensitive to FEN1 perturbation. Collectively, our data indicate that PARP1 is a sensor of unligated Okazaki fragments during DNA replication and facilitates their repair

Multi-Player and Multi-Choice Quantum Game

We investigate a multi-player and multi-choice quantum game. We start from two-player and two-choice game and the result is better than its classical version. Then we extend it to N-player and N-choice cases. In the quantum domain, we provide a strategy with which players can always avoid the worst outcome. Also, by changing the value of the parameter of the initial state, the probabilities for players to obtain the best payoff will be much higher that in its classical version.Comment: 4 pages, 1 figur

Development of 2-(4-pyridyl)-benzimidazoles as PKN2 chemical tools to probe cancer

Kinases are signalling proteins which have proven to be successful targets for the treatment of a variety of diseases, predominantly in cancers. However, only a small proportion of kinases (<20%) have been investigated for their therapeutic viability, likely due to the lack of available chemical tools across the kinome. In this work we describe initial efforts in the development of a selective chemical tool for protein kinase N2 (PKN2), a relatively unexplored kinase of interest in several types of cancer. The most successful compound, 5, has a measured IC50 of 0.064 μM against PKN2, with ca. 17-fold selectivity over close homologue, PKN1

Basics of Superluminal Signals

The paper elucidates the physical basis of experimental results on superluminal signal velocity. It will be made plausible that superluminal signals do not violate the principle of causality but they can shorten the luminal vacuum time span between cause and effect. This amazing behaviour is based on the property that any physical signal has a finite duration.Comment: 11 pages, 8 figure

African trypanosomiasis: Synthesis & SAR enabling novel drug discovery of ubiquinol mimics for trypanosome alternative oxidase

African trypanosomiasis is a parasitic disease affecting 5000 humans and millions of livestock animals in sub-Saharan Africa every year. Current treatments are limited, difficult to administer and often toxic causing long term injury or death in many patients. Trypanosome alternative oxidase is a parasite specific enzyme whose inhibition by the natural product ascofuranone (AF) has been shown to be curative in murine models. Until now synthetic methods to AF analogues have been limited, this has restricted both understanding of the key structural features required for binding and also how this chemotype could be developed to an effective therapeutic agent. The development of 3 amenable novel synthetic routes to ascofuranone-like compounds is described. The SAR generated around the AF chemotype is reported with correlation to the inhibition of T. b. brucei growth and corresponding selectivity in cytotoxic assessment in mammalian HepG2 cell lines. These methods allow access to greater synthetic diversification and have enabled the synthesis of compounds that have and will continue to facilitate further optimisation of the AF chemotype into a drug-like lead

Development of dihydropyrrolopyridinone-based PKN2/PRK2 chemical tools to enable drug discovery

The Protein Kinase N proteins (PKN1, PKN2 and PKN3) are Rho GTPase effectors. They are involved in several biological processes such as cytoskeleton organization, cell mobility, adhesion, and cell cycle. Recently PKNs have been reported as essential for survival in several tumor cell lines, including prostate and breast cancer. Here, we report the development of dihydropyrrolopyridinone-based inhibitors for PKN2 and its closest homologue, PKN1, and their associated structure–activity relationship (SAR). Our studies identified a range of molecules with high potency exemplified by compound 8 with Ki = 8 nM for PKN2 and 14x selectivity over PKN1. Membrane permeability and target engagement for PKN2 were assessed by a NanoBRET cellular assay. Importantly, good selectivity across the wider human kinome and other kinase family members was achieved. These compounds provide strong starting points for lead optimization to PKN1/2 development compounds

Mode of action of DNA-competitive small molecule inhibitors of tyrosyl DNA phosphodiesterase 2

TDP2 is a 5’-tyrosyl DNA phosphodiesterase important for the repair of DNA adducts generated by non-productive (abortive) activity of topoisomerase II. TDP2 facilitates therapeutic resistance to topoisomerase poisons, which are widely used in the treatment of a range of cancer types. Consequently, TDP2 is an interesting target for the development of small molecule inhibitors that could restore sensitivity to topoisomerase-directed therapies. Previous studies identified a class of deazaflavin-based molecules that showed inhibitory activity against TDP2 at therapeutically useful concentrations, but their mode of action was uncertain. We have confirmed that the deazaflavin series inhibits TDP2 enzyme activity in a fluorescence-based assay, suitable for HTS-screening. We have gone on to determine crystal structures of these compounds bound to a ‘humanised’ form of murine TDP2. The structures reveal their novel mode of action as competitive ligands for the binding site of an incoming DNA substrate, and point the way to generating novel and potent inhibitors of TDP2