3d Pi Research Articles

An open-source, 3D printed inkjet DNA synthesizer

Synthetic oligonucleotides have become a fundamental tool in a wide range of biological fields, including synthetic biology, biosensing, and DNA storage. Reliable access to equipment for synthesizing high-density oligonucleotides in the laboratory ensures research security and the freedom of research expansion. In this study, we introduced the Open-Source Inkjet DNA Synthesizer (OpenIDS), an open-source inkjet-based microarray synthesizer that offers ease of construction, rapid deployment, and flexible scalability. Utilizing 3D printing, Arduino, and Raspberry Pi, this newly designed synthesizer achieved robust stability with an industrial inkjet printhead. OpenIDS maintains low production costs and is therefore suitable for self-fabrication and optimization in academic laboratories. Moreover, even non-experts can create and control the synthesizer with a high degree of freedom for structural modifications. Users can easily add printheads or alter the design of the microarray substrate according to their research needs. To validate its performance, we synthesized oligonucleotides on 144 spots on a 15 × 25-mm silicon wafer filled with controlled pore glass. The synthesized oligonucleotides were analyzed using urea polyacrylamide gel electrophoresis.

A regression approach for assessing large molecular drug concentration in breast milk

The development of an effective method for predicting the transfer of biologics from plasma into breast milk is important to ensure the safe use of medications during lactation. The aim of this study was to develop a regression model that could predict the transfer of monoclonal antibodies (mAbs) and Fc-fusion proteins from plasma into breast milk. By searching various databases, a list of eleven mAbs and Fc-fusion proteins with available information of presence in the breast milk was generated. Physicochemical properties such as the isoelectric point (pI), molecular weight (MW), dissociation constant (Kd), and pharmacokinetic (PK) parameters such as clearance (CL), volume of distribution (Vd), and half-life (T1/2) were collected or calculated. A two-variable non-linear regression analysis and a multivariate regression analysis were employed to establish correlation of milk-to-plasma (M/P) ratios with different combinations of two physicochemical properties. The 3D isoelectric point (pI) of the Fv region and the buried surface area (BSA) between the light and heavy chains (LC_HC) were two factors that emerged as a promising predictor of the milk-to-plasma concentration ratio (M/P). The correlation between M/P ratio, 3D pI of Fv region, and BSA_LC_HC was found to be good with R2 of 0.9058. Other combinations of the physicochemical properties did not show a statistically significant correlation. The multivariate regression model was used to predict the MP ratios for 79 different mAbs. We believe that this regression model could serve as a valuable tool to estimate the M/P ratios of mAbs and Fc-fusion proteins. Further model validation is necessary when the M/P ratios of additional biologics are available. This could inform clinical decision-making and improve the safety of large molecule drug use during lactation.

3132 Machine Learning for Prediction of Pathologic Pneumatosis Intestinalis Using CT Scans

OBJECTIVES/SPECIFIC AIMS: This retrospective study aims to create and train machine learning models using a radiomic-based feature extraction method for two classification tasks: benign vs. pathologic PI and operation of benefit vs. operation not needed. The long-term goal of our study is to build a computerized model that incorporates both radiomic features and critical non-imaging clinical factors to improve current surgical decision-making when managing PI patients. METHODS/STUDY POPULATION: Searched radiology reports from 2010-2012 via the UPMC MARS Database for reports containing the term “pneumatosis” (subsequently accounting for negations and age restrictions). Our inclusion criteria included: patient age 18 or older, clinical data available at time of CT diagnosis, and PI visualized on manual review of imaging. Cases with intra-abdominal free air were excluded. Collected CT imaging data and an additional 149 clinical data elements per patient for a total of 75 PI cases. Data collection of an additional 225 patients is ongoing. We trained models for two clinically-relevant prediction tasks. The first (referred to as prediction task 1) classifies between benign and pathologic PI. Benign PI is defined as either lack of intraoperative visualization of transmural intestinal necrosis or successful non-operative management until discharge. Pathologic PI is defined as either intraoperative visualization of transmural PI or withdrawal of care and subsequent death during hospitalization. The distribution of data samples for prediction task 1 is 47 benign cases and 38 pathologic cases. The second (referred to as prediction task 2) classifies between whether the patient benefitted from an operation or not. “Operation of benefit” is defined as patients with PI, be it transmural or simply mucosal, who benefited from an operation. “Operation not needed” is defined as patients who were safely discharged without an operation or patients who had an operation, but nothing was found. The distribution of data samples for prediction task 2 is 37 operation not needed cases and 38 operation of benefit cases. An experienced surgical resident from UPMC manually segmented 3D PI ROIs from the CT scans (5 mm Axial cut) for each case. The most concerning ~10-15 cm segment of bowel for necrosis with a 1 cm margin was selected. A total of 7 slices per patient were segmented for consistency. For both prediction task 1 and prediction task 2, we independently completed the following procedure for testing and training: 1.) Extracted radiomic features from the 3D PI ROIs that resulted in 99 total features. 2.) Used LASSO feature selection to determine the subset of the original 99 features that are most significant for performance of the prediction task. 3.) Used leave-one-out cross-validation for testing and training to account for the small dataset size in our preliminary analysis. Implemented and trained several machine learning models (AdaBoost, SVM, and Naive Bayes). 4.) Evaluated the trained models in terms of AUC and Accuracy and determined the ideal model structure based on these performance metrics. RESULTS/ANTICIPATED RESULTS: Prediction Task 1: The top-performing model for this task was an SVM model trained using 19 features. This model had an AUC of 0.79 and an accuracy of 75%. Prediction Task 2: The top-performing model for this task was an SVM model trained using 28 features. This model had an AUC of 0.74 and an accuracy of 64%. DISCUSSION/SIGNIFICANCE OF IMPACT: To the best of our knowledge, this is the first study to use radiomic-based machine learning models for the prediction of tissue ischemia, specifically intestinal ischemia in the setting of PI. In this preliminary study, which serves as a proof of concept, the performance of our models has demonstrated the potential of machine learning based only on radiomic imaging features to have discriminative power for surgical decision-making problems. While many non-imaging-related clinical factors play a role in the gestalt of clinical decision making when PI presents, we have presented radiomic-based models that may augment this decision-making process, especially for more difficult cases when clinical features indicating acute abdomen are absent. It should be noted that prediction task 2, whether or not a patient presenting with PI would benefit from an operation, has lower performance than prediction task 1 and is also a more challenging task for physicians in real clinical environments. While our results are promising and demonstrate potential, we are currently working to increase our dataset to 300 patients to further train and assess our models. References DuBose, Joseph J., et al. “Pneumatosis Intestinalis Predictive Evaluation Study (PIPES): a multicenter epidemiologic study of the Eastern Association for the Surgery of Trauma.” Journal of Trauma and Acute Care Surgery 75.1 (2013): 15-23. Knechtle, Stuart J., Andrew M. Davidoff, and Reed P. Rice. “Pneumatosis intestinalis. Surgical management and clinical outcome.” Annals of Surgery 212.2 (1990): 160.

Pt-Ni nanoframes functionalized with carbon dots: an emerging class of bio-nanoplatforms.

We designed a unique and novel bio-nanoplatform based on Pt-Ni nanoframes (PNnf) functionalized with carbon dots via the EDC/NHS coupling chemistry. The PNnf with open three-dimensional surfaces exhibited excellent water solubility after polyethylenimine modification. Due to low cytotoxicity and excellent biocompatibility, the bio-nanoplatforms were firstly used for MCF-7 cell imaging in vitro. More importantly, the design strategy can be readily generalized to facilitate other multi-functional bio-nanoplatforms for biological and biomedical applications.

Makerspaces: A Practical Guide for Librarians

I am not a crafty person. I do not enjoy working with my hands all that much. So when I started to read over the book Makerspaces: A Practical Guide for Librarians, the first thing I thought was “I don't think so!” However, the idea is actually a pretty good one. As one librarian who has a makerspace in her library put it: “Not only do we continue the important work of preservation and access that we have done all along, but…libraries will support content creation” (p. 15). All the libraries profiled in the book are either public, community, or academic. No special libraries participated in a survey that the author conducted on makerspaces in libraries in 2013. Looking at it from one perspective, special libraries—or in this case, medical or health sciences libraries—already support content creation when we support our patrons in their, or our own, endeavors to publish research results. Maybe someday we may actually be able to publish the journals or books in our own makerspaces! In any case, many of the libraries use their makerspaces to enhance their schools' curricula, particularly in science, technology, engineering, and medicine (STEM) education, and in problem-based learning. Libraries also conduct workshops and activity programs in their makerspaces, as well as let their patrons use the makerspaces for their own projects. They might start the space because they saw a need that it would fill for their community. They are now participating in maker fairs and camps, and some who have no space in their libraries have a mobile makerspace. According to some of the librarians working in the libraries profiled in the book, not every library will, or can, or should do everything. A makerspace can have anything from knitting supplies and Legos to 3D printers and Raspberry Pi. Depending on space, budget, and your makerspace users, pick what is most popular and work from there. You do not need every piece of equipment or tool; you may be able to use equipment from other departments, if you are an academic library, for instance. Some special considerations include noise, dirt and mess, electricity, safety, and ventilation, as well as space. The Oakland, California, Public Library has a tool lending library (full disclosure: my library is right down the street). As always when a library is thinking of adding a program or service, the staff still looks at space, budget, staffing, patron interest and feedback, measures of success, and so forth. The author, an academic librarian, does fairly well discussing these issues throughout the book in the context of the profiled libraries. I like that the author let the librarians speak about their own libraries. John. J. Burke does a good job of explaining the history and background of making and makerspaces. The results of the survey are included in an appendix. The tables and figures are numerous, although I am not sure they really increase the book's utility. There is a bibliography that includes the references from the chapters; are both necessary? The index is adequate. The author's basic purpose and premise for the book are that every library will become a makerspace in one way or another. And he may be right. While I was working on this review, I read an article about GE starting a makerspace in one of its subsidiaries [1]. If you know nothing about makerspaces or if you would like to start one for your library, this book is a good place to start.

Comparison of 3- and 2-Dimensional Sonographic Techniques for Counting Ovarian Follicles

The purpose of this study was to compare 3-dimensional (3D) and 2-dimensional (2D) ovarian follicle counts and 3D counts using stored volumes between experienced and inexperienced operators. Follicles larger than 5 mm were counted on 1 randomly selected ovary. Two-dimensional follicle counts were compared with stored 3D volumes by the same experienced operator (registered diagnostic medical sonographer [RDMS]). Counts using 3D stored data were compared between the experienced operator and inexperienced operator (principal investigator [PI]). The mean difference in follicle counts was computed, and a 1-sample Student t test was performed to test the hypothesis that the mean of the differences was 0. Comparison of the 2 methods and observers by Bland-Altman plots was used to determine any systematic differences based on the total number of follicles per selected ovary. Mean differences differed from 0 (P < .005) for all 3 comparisons: 2D RDMS versus 3D RDMS, 2D RDMS versus 3D PI, and 3D RDMS versus 3D PI. For the comparison of 2D versus 3D counts done by the RDMS, 5 ovaries (10%) had a difference of more than 5 follicles counted; for the 2D RDMS versus 3D PI, 11 ovaries (22%) had a difference of more than 5 follicles; for the 3D RDMS versus 3D PI, 8 ovaries (16%) had a difference of more than 5 follicles. Mean differences in counts ranged 0.29 to 1.04 for ovaries with 10 or fewer follicles compared with 3.94 to 9.00 for ovaries with more than 10 follicles. Follicle counts using 3D volumes were similar to 2D counts, and 3D follicle counts done by an inexperienced operator were similar to counts done by an experienced sonographer.

Photoluminescence of 1-D Copper(I) Cyanide Chains: A Theoretical Description

Solid copper(I) cyanide occurs as extended one-dimensional chains with interesting photophysical properties. To explain the observed luminescence spectroscopy of CuCN, we report a series of computational studies using short bare and potassium-capped [Cu(n)(CN)(n+1)] (-) (n = 1, 2, 3, 4, 5, and 7) chains as CuCN models. On the basis of TD-DFT calculations of these model chains, the excitation transitions in the UV spectrum are assigned as Laporte-allowed pi-pi transitions from MOs with Cu 3d(pi) and CN pi character to empty MOs with Cu 4p and CN pi* character. Transitions between the HOMO (3d(z)) and LUMO (Cu 4p and CN pi*) are symmetry forbidden and are not assigned to the bands in the excitation spectrum. The emission spectrum is assumed to arise from transitions between the lowest triplet excited state and the ground-state singlet. The lowest energy triplet for the model networks has a bent structure due to distortions to remove the degeneracies in the partially occupied MOs of the linear triplet. The S(0)-T gap for the bent triplet chains is consistent with the emission wavelength for bulk CuCN.

Infrared Spectra of the CH3−MX and CH2−MHX Complexes Formed by Reactions of Laser-Ablated Group 3 Metal Atoms with Methyl Halides

Reactions of laser-ablated group 3 metal atoms with methyl halides have been carried out in excess of Ar during condensation and the matrix infrared spectra studied. The metals are as effective as other early transition metals in providing insertion products (CH3-MX) and higher oxidation state methylidene complexes (CH2-MHX) (X = F, Cl, Br) following alpha-hydrogen migration. Unlike the cases of the group 4-6 metals, the calculated methylidene complex structures show little evidence for agostic distortion, consistent with the previously studied group 3 metal methylidene hydrides, and the C-M bond lengths of the insertion and methylidene complexes are comparable to each other. However, the C-Sc bond lengths are 0.013, 0.025, and 0.029 A shorter for the CH2-ScHX complexes, respectively, and the spin densities are consistent with weak C(2p)-Sc(3d) pi bonding. The present results reconfirm that the number of valence electrons on the metal is important for agostic interaction in simple methylidene complexes.

Dual Room-Temperature Fluorescent and Phosphorescent Emission in 8-Quinolinolate Osmium(II) Carbonyl Complexes: Rationalization and Generalization of Intersystem Crossing Dynamics

A new series of quinolinolate osmium carbonyl complexes were synthesized and characterized by spectroscopic methods. Single-crystal X-ray diffraction studies indicate that these complexes consist of an octahedral ligand arrangement with one chelating quinolinolate, one tfa or halide ligand, and three mutually orthogonal terminal CO ligands. Variation of the substituents on quinolinolate ligands imposes obvious electronic or structural effects, while changing the tfa ligand to an electron-donating iodide slightly increases the charge density on the central osmium atom. These Os(II) complexes show salient dual emissions consisting of fluorescence and phosphorescence, the spectral properties and relaxation dynamics of which have been studied comprehensively. The results, in combination with the theoretical approaches, lead us to propose that the emission mainly originates from the quinolinolate pi pi* state. Both experimental and theoretical approaches generalize various types of intersystem crossing versus those of the tris(quinolinolate) iridium Ir(Q)3, and their relative efficiencies were accessed on the basis of the associated frontier orbital configurations. Our results suggest that [1d(pi)pi* absolute value(H(so))3 pi pi*] (or [3d(pi)pi* absolute value(H(so))1 pi pi*]) in combination with a smaller deltaE(S1-T1) gap (i.e., increasing the MLCT (d(pi)pi*) character) is the main driving force to induce the ultrafast S1 --> T1 intersystem crossing in the third-row transition metal complexes, giving the strong phosphorescent emission.

Spectroscopy of Non-Heme Iron Thiolate Complexes: Insight into the Electronic Structure of the Low-Spin Active Site of Nitrile Hydratase

Detailed spectroscopic and computational studies of the low-spin iron complexes [Fe(III)(S2(Me2)N3 (Pr,Pr))(N3)] (1) and [Fe(III)(S2(Me2)N3 (Pr,Pr))]1+ (2) were performed to investigate the unique electronic features of these species and their relation to the low-spin ferric active sites of nitrile hydratases. Low-temperature UV/vis/NIR and MCD spectra of 1 and 2 reflect electronic structures that are dominated by antibonding interactions of the Fe 3d manifold and the equatorial thiolate S 3p orbitals. The six-coordinate complex 1 exhibits a low-energy S(pi) --> Fe 3d(xy) (approximately 13,000 cm(-1)) charge-transfer transition that results predominantly from the low energy of the singly occupied Fe 3d(xy) orbital, due to pure pi interactions between this acceptor orbital and both thiolate donor ligands in the equatorial plane. The 3d(pi) --> 3d(sigma) ligand-field transitions in this species occur at higher energies (>15,000 cm(-1)), reflecting its near-octahedral symmetry. The Fe 3d(xz,yz) --> Fe 3d(xy) (d(pi) --> d(pi)) transition occurs in the near-IR and probes the Fe(III)-S pi-donor bond; this transition reveals vibronic structure that reflects the strength of this bond (nu(e) approximately 340 cm(-1)). In contrast, the ligand-field transitions of the five-coordinate complex 2 are generally at low energy, and the S(pi) --> Fe charge-transfer transitions occur at much higher energies relative to those in 1. This reflects changes in thiolate bonding in the equatorial plane involving the Fe 3d(xy) and Fe 3d(x2-y2) orbitals. The spectroscopic data lead to a simple bonding model that focuses on the sigma and pi interactions between the ferric ion and the equatorial thiolate ligands, which depend on the S-Fe-S bond angle in each of the complexes. These electronic descriptions provide insight into the unusual S = 1/2 ground spin state of these complexes: the orientation of the thiolate ligands in these complexes restricts their pi-donor interactions to the equatorial plane and enforces a low-spin state. These anisotropic orbital considerations provide some intriguing insights into the possible electronic interactions at the active site of nitrile hydratases and form the foundation for further studies into these low-spin ferric enzymes.

The photophysics of fac-[Re(CO)3(dppz)(py)]+ in CH3CN: a comparative picosecond flash photolysis, transient infrared, transient resonance Raman and density functional theoretical study.

The photophysical properties of fac-[Re(CO)3(dppz)(py)]+ (1, where dppz = dipyrido[3,2-a: 2',3'-c]phenazine) in CH3CN have been investigated using a series of complementary techniques including visible and infrared transient absorption and resonance Raman spectroscopy on the picosecond and nanosecond timescales. The results confirm previous reports that the lowest-lying emissive state in 1 is a triplet intra-ligand (3IL) state localised on the dppz ligand and have provided detailed information on the dynamics of 1 upon photoexcitation, including the relative energies of the excited state species encountered and the electronic distribution within these. If the dppz ligand is viewed in terms of phenanthroline (phen) and phenazine (phz) moieties, the emissive state is probably more accurately described as a 3 pi-->pi *(phz) IL state. The picosecond studies have shown that this emissive state is formed, at least in part, within 30 ps of excitation from a precursor, which is possibly a 3 pi-->pi *(phen) IL state. On the nanosecond timescale, TRIR has been employed to elucidate further dynamics and reveal the presence of an energetically close-lying state in equilibrium with the emissive state. This has tentatively been assigned as being 3d pi(Re)-->pi *(phz) metal-to-ligand charge transfer (MLCT) in nature. A summary of the photophysics is proposed in the form of a Jablonski scheme. Time dependent density functional theory (TD-DFT) calculations support the relative ordering and suggested electronic character of the excited state species involved.

Electronic structure of 3d[M(H2O)6](3+) ions from Sc(III) to Fe(III): a quantum mechanical study based on DFT computations and natural bond orbital analyses.

The metal-donor atom bonding along the series of 3d[M(H2O)6](3+) ions from Sc(3+) to Fe(3+) has been investigated by density-functional calculations combined with natural localized bond orbital analyses. The M-OH(2) bonds were considered as donor-acceptor bonds, and the contributions coming from the metal ion's 3d sigma-, 3d pi-, and 4s sigma-interactions were treated individually. In this way, the total amount of charge transferred from the water oxygen-donor atoms toward the appropriate metal orbitals could be analyzed in a straightforward manner. One result obtained along these lines is that the overall extent of ligand-to-metal charge transfer shows a strong correlation to the hydration enthalpies of the aqua metal ions. If the contributions to the total ligand-to-metal ion charge transfer are divided into sigma- and pi-contributions, it turns out that Cr(3+) is the best sigma-acceptor, but its pi-accepting abilities are the weakest along the series. Fe(3+) is found to be the best pi-acceptor among the 3d hexaaqua ions studied. Its aptitude to accept sigma-electron density is the second weakest along the series and only slightly higher than that of Sc(3+) (the least sigma-acceptor of all ions) because of the larger involvement of the Fe(3+) 4s orbital in sigma-bonding. The strengths of the three types of bonding interactions have been correlated with the electron affinities of the different metal orbitals. Deviations from the regular trends of electron affinities along the series were found for those [M(H2O)6](3+) ions that are subject to Jahn-Teller distortions. In these cases (d(1) = [Ti(H2O)6](3+), d(2) = [V(H2O)6](3+), and d(4) = [Mn(H2O)6](3+)), ligand-to-metal charge transfer is prevented to go into those metal orbitals that contain unpaired d electrons. A lowering of the complex symmetry is observed and coupled with the following variations: The Ti(3+)- and V(3+)-hexaaqua ions switch from T(h)() to C(i)() symmetry while the Mn(3+)-hexaaqua ion moves to D(2)(h)() symmetry. The loss of orbital overlap leading to a diminished ligand-to-metal charge transfer toward the single occupied metal orbitals is compensated by amplified bonding interactions of the ligand orbitals with the unoccupied metal orbitals to some extent.

Rotationally induced transitions in close encounters of one-electron collisional systems: the three-state problem

Transitions induced by rotation of the internuclear axis in close collisions of atomic particles at low energies are investigated within the one-electron united-atom approximation. The three-state problem ( sigma to pi , delta transitions) is treated in more detail. Effects arising as a consequence of a different choice of classical trajectories of the nuclei are demonstrated in the example of 3d sigma to 3d pi , 3d delta transitions, contributing to the Li3++H to Li2++H+ charge-exchange reaction.

Variational translation factors for He2+-H collisions

A satisfactory molecular perturbed-stationary-states treatment of one-electron heteronuclear asymmetric charge transfer is derived. Electronic translation factors and their inherent switching functions are determined variationally. Specific consideration is given to the 2p sigma , 2p pi , 3d sigma , 3d pi and 2s sigma states of the HeH2+ molecular ion.

Molecular treatment of charge transfer in He2+-H collisions

A multistate molecular approach to the He2+-H collision is applied within an impact parameter perturbed-stationary-states formulation. Spurious long-range couplings are avoided and Galilean invariance is enforced by the inclusion of electronic momentum translation factors determined variationally within an Euler-Lagrange formalism (Crothers and Todd). Well defined, symmetrised radial and rotational coupling matrix elements are employed in the 4He2+ impact energy range 2-25 keV in a five-state (2p sigma , 2p pi , 3d sigma , 3d pi , 2s sigma ) calculation of total and 4He+ (2s) capture cross sections. They are also used over the 0-3 degrees laboratory scattering angle range to calculate elastic and inelastic differential cross sections at a 3He2+ impact energy of 4.5 keV. Results for the capture probability at 1.2 degrees agree reasonably well with the experiment of Keever and Everhart (1966) over the 3He2+ 2-20 keV energy range and are compared with previous molecular calculations.

Influence of nuclear structure on widths of π-atomic terms

The authors calculate the widths of 2p and 3d pi -atomic states in the nuclei 12C, 16O, 32S, 40Ar, 40-48Ca, 46-50Ti and 52Cr assuming the 'two-nucleon' mechanism to be the doorway process for nuclear pion absorption. The results are in good agreement with experiment.

3dπ-2pπ radial coupling in symmetric and near-symmetric heavy-ion-atom collisions

Presents new evidence for a sharing of projectile 2p vacancies in heavy-ion-atom collisions, Z1 approximately=Z2 approximately 35 and E/M<or approximately=0.5 MeV/amu. The sharing is effected by 3d pi -2p pi radial coupling and can be described through a function WL=(1+exp(1.79XL))-1, analogous to 2p sigma -1s sigma K-vacancy sharing. XL is a simple function of the projectile velocity and the 2p binding energies of the projectile and target atoms. The data may be used to show that the region of internuclear distances where 3d pi -2p pi radial coupling occurs is spatially distinct from the region of 2p pi -2p sigma rotational coupling.