Prediction of zwitterion hydration and ion association properties using machine learning.

Molecular dynamics simulations were performed to study the hydration and ion association properties of a library of zwitterionic molecules with varying charged moieties and spacer chemistries in pure water and with Na+ and Cl- ions. The structure and dynamics of associations were calculated using the radial distribution and residence time correlation function. Resulting association properties are used as target variables for a machine learning model, with cheminformatic descriptors of the molecule subunits used as descriptors. Prediction of hydration properties revealed that steric and hydrogen bonding descriptors were of greatest importance and there was influence from the cationic moiety on the anionic moiety hydration properties. Ion association properties prediction performed poorly, which is attributed to the role of hydration layers in ion association dynamics. This study is the first to quantitatively describe the influence of subunit chemistry on hydration and ion association properties of zwitterions. These quantitative descriptions supplement prior studies of zwitterion association and previously described design principles.

Clinical spectrum of atypical fibroxanthoma and undifferentiated pleomorphic sarcoma in solid organ transplant recipients: a collective experience.

BACKGROUND: Atypical fibroxanthoma (AFX) and undifferentiated pleomorphic sarcoma (UPS) are uncommon, spindle cell cutaneous malignancies. Solid organ transplant recipients (SOTRs) are immunosuppressed and therefore have a higher incidence of cutaneous malignancies. OBJECTIVE: We describe the clinical spectrum of AFX and a more-aggressive, deeper variant, UPS, in SOTRs. MATERIALS AND METHODS: A retrospective chart review of AFX and UPS in SOTRs was implemented. Cases from Vanderbilt University, Emory University, Mayo Clinic-Jacksonville, and University of Rochester were included. A literature search included previously published cases. RESULTS: The average age of SOTRs at time of tumor presentation was younger than typically seen in immunocompetent patients for AFX. Rates of local recurrences and metastases were higher in the SOTRs than is noted in the immunocompetent literature. Rates of recurrence were higher in those treated with excision than in those treated with Mohs micrographic surgery (MMS). CONCLUSION: AFX and UPS may have a greater risk for recurrence, metastases, and mortality in SOTRs, in whom early treatment with MMS may demonstrate certain advantages in terms of minimizing risk of recurrence and metastasis. UPS and recurrent tumors should be staged appropriately and may respond to adjuvant radiation therapy and reduction of immunosuppression. Immunohistochemical evaluation is recommended to exclude other spindle cell tumors.

Thermoplastic polyurethane with controllable degradation and critical anti-fouling properties.

Bioresorbable polymers, including polyesters and polypeptides, are being widely used in the medical field. However, these materials still suffer from some long-standing challenges, such as material-induced blood coagulation, foreign body response, non-adjustable degradation rate, and absence of elastic properties. In this work, we explored a new approach to address these challenges by incorporating critical anti-fouling, improved mechanical and controllable degradation properties into the existing bioresorbable polymers. We synthesized a set of zwitterionic thermoplastic polyurethanes, which consist of degradable polycaprolactone diols as soft segments and faster hydrolyzable carboxybetaine (CB) diols as chain extenders. Differential scanning calorimetry and temperature sweep rheology revealed thermal transition performance and thermoplastic behavior of the polymers. The calorimetric study observed that CB-based chain extender played a critical role in the crystallization process by affecting the structure and crystallization temperature. Cell attachment study demonstrated that the degradable zwitterionic polyurethane surfaces highly resist cell attachment even after being submerged in 100% fetal bovine serum for two weeks. The gold standard PEG-based degradable polyurethane showed the initial resistance to the cell attachment for one day and then failed after three days. This work clearly shows that the adaption of existing materials with slightly better anti-fouling properties is unlikely to solve these long-lasting challenges. Our design approach and the material platform with critical anti-fouling properties and other desired tunable properties show the potential to address these complications associated with existing bioresorbable polymers. This method can be adapted to design customized bioresorbable polymers for a wide range of applications, including implantable biomedical devices and drug delivery.

Winning the fight against biofilms: the first six-month study showing no biofilm formation on zwitterionic polyurethanes.

Biofilms have been a long-standing challenge for healthcare, water transport, and many other industries. They lead to bacterial growth and infections in animals, food products, and humans, cause premature removal of the implanted materials or devices from patients, and facilitate fouling and corrosion of metals. Despite some published and patented methods on minimizing the effects of biofilms for a short period (less than two weeks), there exists no successful means to mitigate or prevent the long-term formation of biofilms. It is even more challenging to integrate critical anti-fouling properties with other needed physical and chemical properties for a range of applications. In this study, we developed a novel approach for combining incompatible, highly polar anti-fouling groups with less polar, mechanically modifying groups into one material. A multifunctional carboxybetaine precursor was designed and introduced into polyurethane. The carboxybetaine precursors undergo rapid, self-catalyzed hydrolysis at the water/material interface and provide critical anti-fouling properties that lead to undetectable bacterial attachment and zero biofilm formation after six months of constant exposure to Pseudomonas aeruginosa and Staphylococcus epidermidis under the static condition in a nutrient-rich medium. This zwitterionic polyurethane is the first material to demonstrate both critical anti-biofilm properties and tunable mechanical properties and directly validates the unproven anti-fouling strategy and hypothesis for biofilm formation prevention. This approach of designing 'multitasking materials' will be useful for the development of next generation anti-fouling materials for a variety of applications.

Effect of vertical disparities on depth representation in macaque monkeys: MT physiology and behavior.

Horizontal binocular disparities provide information about the distance of objects relative to the point of ocular fixation and must be combined with an estimate of viewing distance to recover the egocentric distance of an object. Vergence angle and the gradient of vertical disparities across the visual field are thought to provide independent sources of viewing distance information based on human behavioral studies. Although the effect of vergence angle on horizontal disparity selectivity in early visual cortex has been examined (with mixed results), the effect of the vertical disparity field has not been explored. We manipulated the vertical disparities in a large random-dot stimulus to simulate different viewing distances, and we examined the effect of this manipulation on both the responses of neurons in the middle temporal (MT) area and on the psychophysical performance of the animal in a curvature discrimination task. We report here that alterations to the vertical disparity field have no effect on the horizontal disparity tuning of MT neurons. However, the same manipulation strongly and systematically biases the monkey's judgments of curvature, consistent with previous human studies. We conclude that monkeys, like humans, make use of the vertical disparity field to estimate viewing distance, but that the physiological mechanisms for this effect occur either downstream of MT or in a different pathway.