Microfluidic ion stripper for removal of trifluoroacetic acid from mobile phases used in HILIC-MS of intact proteins

© 2021, The Author(s).Trifluoroacetic acid (TFA) is commonly used as mobile phase additive to improve retention and peak shape characteristics in hydrophilic interaction liquid chromatography (HILIC) of intact proteins. However, when using electrospray ionization-mass spectrometry (ESI-MS) detection, TFA may cause ionization suppression and adduct formation, leading to reduced analyte sensitivity. To address this, we describe a membrane-based microfluidic chip with multiple parallel channels for the selective post-column removal of TFA anions from HILIC. An anion-exchange membrane was used to physically separate the column effluent from a stripper flow solution comprising acetonitrile, formic acid, and propionic acid. The exchange of ions allowed the post-column removal of TFA used during HILIC separation of model proteins. The multichannel design of the device allows the use of flow rates of 0.2 mL/min without the need for a flow splitter, using mobile phases containing 0.1% TFA (13 mM). Separation selectivity and efficiency were maintained (with minor band broadening effects) while increasing the signal intensity and peak areas by improving ionization and reducing TFA adduct formation. Graphical abstract: [Figure not available: see fulltext.

Recommended patient information sheet on the impact of haematopoietic cell transplantation on sexual functioning and sexuality

Sexual concerns are common after haematopoietic cell transplantation (HCT). Exposure to total body irradiation (TBI), alkylating agent and graft versus host disease (GvHD) can all affect sexual function, leading to problems in sexual desire, arousal and the orgasm phase of the sexual response cycle. In high-risk haematological malignancies, such as acute leukaemia and myelodysplastic syndromes, HCT often offers the highest chance for long-term survival. In addition, these haematological diseases and HCT can have an impact on body image, self-esteem, (sexual) relationship and psychosocial factors, all of which are able to affect sexuality and sexual function. Five years post HCT, 80% of the female survivors and 46% of the male survivors report sexual dysfunction. It has been shown that these patients cope better after having discussed sexual health. While healthcare providers (HCPs) have the resp

Spectral up- and downshifting of Akhmediev breathers under wind forcing

We experimentally and numerically investigate the effect of wind forcing on the spectral dynamics of Akhmediev breathers, a wave-type known to model the modulation instability. We develop the wind model to the same order in steepness as the higher order modifcation of the nonlinear Schroedinger equation, also referred to as the Dysthe equation. This results in an asymmetric wind term in the higher order, in addition to the leading order wind forcing term. The derived model is in good agreement with laboratory experiments within the range of the facility's length. We show that the leading order forcing term amplifies all frequencies equally and therefore induces only a broadening of the spectrum while the asymmetric higher order term in the model enhances higher frequencies more than lower ones. Thus, the latter term induces a permanent upshift of the spectral mean. On the other hand, in contrast to the direct effect of wind forcing, wind can indirectly lead to frequency downshifts, due to dissipative effects such as wave breaking, or through amplification of the intrinsic spectral asymmetry of the Dysthe equation. Furthermore, the definitions of the up- and downshift in terms of peak- and mean frequencies, that are critical to relate our work to previous results, are highlighted and discussed.Comment: 30 pages, 11 figure

Spin-orbit interaction in InSb nanowires

We use magnetoconductance measurements in dual-gated InSb nanowire devices together with a theoretical analysis of weak antilocalization to accurately extract spin-orbit strength. In particular, we show that magnetoconductance in our three-dimensional wires is very different compared to wires in two-dimensional electron gases. We obtain a large Rashba spin-orbit strength of $0.5 -1\,\text{eV\r{A}}$ corresponding to a spin-orbit energy of $0.25-1\,\text{meV}$. These values underline the potential of InSb nanowires in the study of Majorana fermions in hybrid semiconductor-superconductor devices.Comment: Version as accepted for publication as a Rapid in Phys. Rev.

Self-Reported Sexual Function in Sexually Active Male Hodgkin Lymphoma Survivors

Introduction: Unambiguous data on sexual dysfunction after Hodgkin lymphoma (HL) treatment are scarce. Aims: To form a baseline in this area, we compared patient-reported sexual function in sexually active male HL survivors in complete remission with a sexually active, age-matched, male Dutch sample population. Furthermore, we explored whether sociodemographic and clinical factors were associated with sexual dysfunction in HL survivors and investigated whether reporting to perceive sexual problems was indicative for sexual dysfunction. Methods: This cross-sectional study included male patients with HL who were treated with chemotherapy and age-matched sexually active males. Main outcome measures: Outcome measures included the internationally validated International Index of Erectile Function (IIEF) and self-reported sexual problems by adding 3 items to the study-specific questionnaire. Results: Erectile dysfunction (ED) occurred in 23.3% of the HL survivors vs in 23.0% of controls: respectively 13.3% and 12.3% had moderate to severe ED. However, more HL survivors positively answered the question whether they did perceive sexual problems than controls (20.0% vs 7.0%; P ¼ .087). More patients treated with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procabazine, and prednisone (BEACOPP) had sexual problems 33.3% vs 8.3% who were treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (P ¼ .057). Importantly, we found that the mean IIEF score for erectile function was 15.7 in HL survivors who reported to perceive sexual problems (moderate ED) vs 28.3 (normal) in those without perceiving sexual problems. Conclusion: In general, sexual function of male HL survivors is comparable to that of matched normal cont

Potential of poly(styrene-co-divinylbenzene) monolithic columns for the LC-MS analysis of protein digests

Two polystyrene-based capillary monolithic columns of different length (50 and 250 mm) were used to evaluate the effects of column length on gradient separation of protein digests. A tryptic digest of a 9-protein mixture was used as a test sample. Peak capacities were determined from selected extracted ion chromatograms, and tandem mass spectrometry data were used for database matching using the MASCOT search engine. Peak capacities and protein identification scores were higher for the long column with all gradients. Peak capacities appear to approach a plateau for longer gradient times; maximum peak capacity was estimated to be 294 for the short column and 370 for the long column. Analyses with similar gradient slope produced a ratio of the peak capacities of 3.36 for the long and the short column, which is slightly higher than the expected value of the square root of the column length ratio. The use of a longer monolith improves peptide separation, as reflected by higher peak capacity, and also increases protein identification, as observed from higher identification scores and a larger number of identified peptides. Attention has also been paid to the peak production rate (PPR, peak capacity per unit time). For short analysis times, the short column produces a higher PPR, while for analysis times longer than 40 min, the PPR of the 250-mm column is higher

Controlled ultraviolet (UV) photoinitiated fabrication of monolithic porous layer open tubular (monoPLOT) capillary columns for chromatographic applications

An automated column fabrication technique that is based on a ultraviolet (UV) light-emitting diode (LED) array oven, and provides precisely controlled "in-capillary" ultraviolet (UV) initiated polymerization at 365 nm, is presented for the production of open tubular monolithic porous polymer layer capillary (monoPLOT) columns of varying length, inner diameter (ID), and porous layer thickness. The developed approach allows the preparation of columns of varying length, because of an automated capillary delivery approach, with precisely controlled and uniform layer thickness and monolith morphology, from controlled UV power and exposure time. The relationships between direct exposure times, intensity, and layer thickness were determined, as were the effects of capillary delivery rate (indirect exposure rate), and multiple exposures on the layer thickness and axial distribution. Layer thickness measurements were taken by scanning electron microscopy (SEM), with the longitudinal homogeneity of the stationary phase confirmed using scanning capacitively coupled contactless conductivity detection (sC(4)D). The new automated UV polymerization technique presented in this work allows the fabrication of monoPLOT columns with a very high column-to-column production reproducibility, displaying a longitudinal phase thickness variation within ±0.8% RSD (relative standard deviation)