Heavy element incorporation in nitroimidazole radiosensitizers: molecular-level insights into fragmentation dynamics.

The present study investigates the photofragmentation behavior of iodine-enhanced nitroimidazole-based radiosensitizer model compounds in their protonated form using near-edge X-ray absorption mass spectrometry and quantum mechanical calculations. These molecules possess dual functionality: improved photoabsorption capabilities and the ability to generate species that are relevant to cancer sensitization upon photofragmentation. Four samples were investigated by scanning the generated fragments in the energy regions around C 1s, N 1s, O 1s, and I 3d-edges with a particular focus on NO2+ production. The experimental summed ion yield spectra are explained using the theoretical near-edge X-ray absorption fine structure spectrum based on density functional theory. Born-Oppenheimer-based molecular dynamics simulations were performed to investigate the fragmentation processes.

Shell-dependent photofragmentation dynamics of a heavy-atom-containing bifunctional nitroimidazole radiosensitizer.

Radiation therapy uses ionizing radiation to break chemical bonds in cancer cells, thereby causing DNA damage and leading to cell death. The therapeutic effectiveness can be further increased by making the tumor cells more sensitive to radiation. Here, we investigate the role of the initial halogen atom core hole on the photofragmentation dynamics of 2-bromo-5-iodo-4-nitroimidazole, a potential bifunctional radiosensitizer. Bromine and iodine atoms were included in the molecule to increase the photoionization cross-section of the radiosensitizer at higher photon energies. The fragmentation dynamics of the molecule was studied experimentally in the gas phase using photoelectron-photoion-photoion coincidence spectroscopy and computationally using Born-Oppenheimer molecular dynamics. We observed significant changes between shallow core (I 4d, Br 3d) and deep core (I 3d) ionization in fragment formation and their kinetic energies. Despite the fact, that the ions ejected after deep core ionization have higher kinetic energies, we show that in a cellular environment, the ion spread is not much larger, keeping the damage well-localized.

X-ray Induced Fragmentation of Protonated Cystine.

We demonstrate site-specific X-ray induced fragmentation across the sulfur L-edge of protonated cystine, the dimer of the amino acid cysteine. Ion yield NEXAFS were performed in the gas phase using electrospray ionization (ESI) in combination with an ion trap. The interpretation of the sulfur L-edge NEXAFS spectrum is supported by Restricted Open-Shell Configuration Interaction (ROCIS) calculations. The fragmentation pathway of triply charged cystine ions was modeled by Molecular Dynamics (MD) simulations. We have deduced a possible pathway of fragmentation upon excitation and ionization of S 2p electrons. The disulfide bridge breaks for resonant excitation at lower photon energies but remains intact upon higher energy resonant excitation and upon ionization of S 2p. The larger fragments initially formed subsequently break into smaller fragments.

Electrotactile Feedback for the Discrimination of Different Surface Textures Using a Microphone.

Most commercial prosthetic hands lack closed-loop feedback, thus, a lot of research has been focusing on implementing sensory feedback systems to provide the user with sensory information during activities of daily living. This study evaluates the possibilities of using a microphone and electrotactile feedback to identify different textures. A condenser microphone was used as a sensor to detect the friction sound generated from the contact between different textures and the microphone. The generated signal was processed to provide a characteristic electrical stimulation presented to the participants. The main goal of the processing was to derive a continuous and intuitive transfer function between the microphone signal and stimulation frequency. Twelve able-bodied volunteers participated in the study, in which they were asked to identify the stroked texture (among four used in this study: Felt, sponge, silicone rubber, and string mesh) using only electrotactile feedback. The experiments were done in three phases: (1) Training, (2) with-feedback, (3) without-feedback. Each texture was stroked 20 times each during all three phases. The results show that the participants were able to differentiate between different textures, with a median accuracy of 85%, by using only electrotactile feedback with the stimulation frequency being the only variable parameter.

The rubber hand illusion evaluated using different stimulation modalities.

Tactile feedback plays a vital role in inducing ownership and improving motor control of prosthetic hands. However, commercially available prosthetic hands typically do not provide tactile feedback and because of that the prosthetic user must rely on visual input to adjust the grip. The classical rubber hand illusion (RHI) where a brush is stroking the rubber hand, and the user's hidden hand synchronously can induce ownership of a rubber hand. In the classic RHI the stimulation is modality-matched, meaning that the stimulus on the real hand matches the stimulus on the rubber hand. The RHI has also been used in previous studies with a prosthetic hand as the "rubber hand," suggesting that a hand prosthesis can be incorporated within the amputee's body scheme. Interestingly, previous studies have shown that stimulation with a mismatched modality, where the rubber hand was brushed, and vibrations were felt on the hidden hand also induced the RHI. The aim of this study was to compare how well mechanotactile, vibrotactile, and electrotactile feedback induced the RHI in able-bodied participants and forearm amputees. 27 participants with intact hands and three transradial amputees took part in a modified RHI experiment. The rubber hand was stroked with a brush, and the participant's hidden hand/residual limb received stimulation with either brush stroking, electricity, pressure, or vibration. The three latter stimulations were modality mismatched with regard to the brushstroke. Participants were tested for ten different combinations (stimulation blocks) where the stimulations were applied on the volar (glabrous skin), and dorsal (hairy skin) sides of the hand. Outcome was assessed using two standard tests (questionnaire and proprioceptive drift). All types of stimulation induced RHI but electrical and vibration stimulation induced a stronger RHI than pressure. After completing more stimulation blocks, the proprioceptive drift test showed that the difference between pre- and post-test was reduced. This indicates that the illusion was drifting toward the rubber hand further into the session.

Clarifying the Adsorption of Triphenylamine on Au(111): Filling the HOMO-LUMO Gap.

In this article, we analyze the electronic structure modifications of triphenylamine (TPA), a well-known electron donor molecule widely used in photovoltaics and optoelectronics, upon deposition on Au(111) at a monolayer coverage. A detailed study was carried out by synchrotron radiation-based photoelectron spectroscopy, near-edge X-ray absorption fine structure (NEXAFS) spectroscopy, scanning tunneling microscopy (STM), and ab initio calculations. We detect a new feature in the pre-edge energy region of the N K-edge NEXAFS spectrum that extends over 3 eV, which we assign to transitions involving new electronic states. According to our calculations, upon adsorption, a number of new unoccupied electronic states fill the energy region between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) of the free TPA molecule and give rise to the new feature in the pre-edge region of the NEXAFS spectrum. This finding highlights the occurrence of a considerable modification of the electronic structure of TPA. The appearance of new states in the HOMO-LUMO gap of TPA when adsorbed on Au(111) has crucial implications for the design of molecular nanoelectronic devices based on similar donor systems.

Touch on predefined areas on the forearm can be associated with specific fingers: Towards a new principle for sensory feedback in hand prostheses.

OBJECTIVE: Currently available hand prostheses lack sensory feedback. A "phantom hand map", a referred sensation, on the skin of the residual arm is a possible target to provide amputees with non-invasive somatotopically matched sensory feedback. How-ever, not all amputees experience a phantom hand map. The aim of this study was to explore whether touch on predefined areas on the forearm can be associated with specific fingers. DESIGN: A longitudinal cohort study. SUBJECTS: A total of 31 able-bodied individuals. METHODS: A "tactile display" was developed consisting of 5 servo motors, which provided the user with mechanotactile stimulus. Predefined pressure points on the volar aspect of the forearm were stimulated during a 2-week structured training period. RESULTS: Agreement between the stimulated areas and the subjects' ability to discriminate the stimulation was high, with a distinct improvement up to the third training occasion, after which the kappa score stabilized for the rest of the period. CONCLUSION: It is possible to associate touch on intact skin on the forearm with specific fingers after a structured training period, and the effect persisted after 2 weeks. These results may be of importance for the development of non-invasive sensory feedback systems in hand prostheses.

A review of invasive and non-invasive sensory feedback in upper limb prostheses.

INTRODUCTION: The constant challenge to restore sensory feedback in prosthetic hands has provided several research solutions, but virtually none has reached clinical fruition. A prosthetic hand with sensory feedback that closely imitates an intact hand and provides a natural feeling may induce the prosthetic hand to be included in the body image and also reinforces the control of the prosthesis. Areas covered: This review presents non-invasive sensory feedback systems such as mechanotactile, vibrotactile, electrotactile and combinational systems which combine the modalities; multi-haptic feedback. Invasive sensory feedback has been tried less, because of the inherent risk, but it has successfully shown to restore some afferent channels. In this review, invasive methods are also discussed, both extraneural and intraneural electrodes, such as cuff electrodes and transverse intrafascicular multichannel electrodes. The focus of the review is on non-invasive methods of providing sensory feedback to upper-limb amputees. Expert commentary: Invoking embodiment has shown to be of importance for the control of prosthesis and acceptance by the prosthetic wearers. It is a challenge to provide conscious feedback to cover the lost sensibility of a hand, not be overwhelming and confusing for the user, and to integrate technology within the constraint of a wearable prosthesis.