Direct Insertion Research Articles

Insertion of ammonia into alkenes to build aromatic N-heterocycles

Ammonia is one of the most abundant and simple nitrogen sources with decent stability and reactivity. Direct insertion of ammonia into a carbon skeleton is an ideal approach to building valuable N-heterocycles for extensive applications with unprecedented atom and step economy. Here, we show an electrochemical dehydrogenative method in which ammonia is inserted directly into alkenes to build aromatic N-heterocycles in a single step without the use of any external oxidant. This new approach achieves 98–99.2% atom economy with hydrogen as the only byproduct. Quinoline and pyridine with diverse substitutions are readily available. In this work, electrochemistry was used to drive a 4-electron oxidation reaction that is hard to access by other protocols, providing a parallel pathway to nitrene chemistry. In a tandem transformation that included three distinct electrochemical processes, the insertion of ammonia further showcased the tremendous potential to manipulate heterocycles derived from Hantzsch ester to diazine via pyridine and pyrrole.

DCITI-Seq: droplet combinational indexed transposon insertion sequencing.

The rapid development of high-throughput parallel sequencing poses new challenges for large-scale barcoding and sequencing library construction. Here, we present droplet combinational indexed transposon insertion sequencing (dCITI-Seq), in which samples are indexed by the direct insertion of index-containing adaptors through transposition. The random combination of two sets of adaptors with known barcodes and massively parallel transposition was realized via a robust droplet pairing and merging platform. This strategy potentially enlarges the indexing capacity and decreases index crosstalk. Also, dCITI-Seq exhibited a lower GC base preference than conventional in-tube transposition library preparation. With a custom bioinformatic processing, it could be further applied to large-scale single-cell sequencing.

Formation of mononuclear N,O-chelate zirconium complexes by direct insertion of epoxide into tetrakis(dimethylamido)zirconium: highly promising approach for developing an ALD precursor of ZrO2 thin films.

A zirconium complex containing an N,O-chelate and alkylamide ligand has great potential for application in atomic layer deposition (ALD). However, the synthesis of this mononuclear Zr complex remains a major challenge because of the highly electrophilic nature and rich coordination of the Zr(IV) atom. Herein, a nonclassical and highly effective route for synthesizing the mononuclear N,O-chelate Zr complex was envisaged and verified using rationally designed reactions, involving the ring-opening insertion of epoxide into tetrakis(dimethylamido)zirconium(IV) (TDMAZ) at room temperature. To the best of our knowledge, very few studies in which mononuclear Zr complexes comprising alkylamide in combination with aminoalkoxide are structurally characterized. This method is extremely simple, atom economical, and easily scalable. Importantly, the produced precursor complex enables ALD of ZrO2 at a satisfactory growth rate (0.93 Å per cycle), close to that of the commercial ALD precursor CpZr(NMe2)3 (0.9 Å per cycle).

An empirical study on V2X radio coverage using leaky coaxial cables in road crash barriers

For current and future automated driving functions, the radio availability of broadband hybrid networking services (e.g. digital broadcasting, mobile radio, dedicated short range communication) is a prerequisite for continuous V2X information exchange. The supply focus for this is explicitly the road route with its lanes. The application of antenna-based solutions for such longitudinal radio cells with hybrid telematics services is expensive from the installation point of view and can only be adapted to new future telematics standards with great effort. A more suitable solution for such longitudinally shaped radio cells for road routes are leaky coaxial cables (LCX), which are already successfully used for tunnel solutions, for example. The paper discusses the installation and radio implementation of broadband LCX solutions (up to 6 GHz) in terms of simulation and surveying. The integration of the LCX into the crash barrier is favored due to low installation effort and easy upgradeability. An installation was realized on an automotive test fields, where preliminary empirical results for radio simulation and coverage were obtained. Based on the simulations and evaluation measurements, it can be shown that the propagated coverage approach is sustainable over all radiated services. Further solution approaches such as the direct insertion of LCX into the roadway and the derivation of vehicle location information are discussed in the outlook of the paper.

Abstract P258: CBX-12 (alphalexTM-exatecan) sensitizes tumors to immune checkpoint blockade in an antigen agnostic manner by immune activation

Abstract Immune checkpoint blockade (ICB) in combination with chemotherapy is standard of care for several solid tumors. However, potent chemotherapies such as topoisomerase inhibitors can result in severe dose-limiting toxicities requiring dose reduction, limiting their efficacy. Moreover, leukocytopenia from chemotherapy induces immunosuppression that further limits the full potential of combinations with ICB. The use of targeted chemotherapies such as antibody-drug conjugates (ADCs) demonstrate potential synergy with ICB, however are limited to a defined subset of patients with tumors expressing the target antigen. Cybrexa has reported the development of CBX-12, a peptide-drug conjugate consisting of alphalexTM-exatecan (1). Rather than targeting a specific antigen, alphalexTM consists of a unique variant of pH-Low Insertion Peptide (pHLIP®; 2-4) which targets the low pH environment of the tumor, a universal feature characteristic of all tumors due to the Warburg effect. The alphalexTM component of CBX-12 forms an alpha helix only in low pH conditions, allowing for directional insertion of the peptide within the cancer cell membrane, delivery of C-terminally linked exatecan across the membrane, and subsequent intracellular release of active exatecan via glutathione reduction of the linker, thereby allowing for tumor-specific intracellular delivery in an antigen-independent manner. Here we evaluated the potential for CBX-12 to effectively synergize with PD1 and CTLA4 blockade in multiple syngeneic mouse models without requirement for tumor specific antigens. We found that CBX-12/ICB combination treatment significantly delayed tumor growth, improved survival and led to complete tumor regressions. Mice cured with combined CBX-12/ICB therapy demonstrated formation of long-term immunological memory after in vivo and ex vivo tumor rechallenge. The ability of CBX-12 to induce immunogenic cell death was confirmed by vaccinating syngeneic mice with CBX-12 treated tumor cells and subsequent tumor rechallenge, which demonstrated near total anti-tumor immunity induced by CBX-12. Together, these preclinical data demonstrate the potential for CBX-12 to enhance tumor immunogenicity and potentiate the efficacy of ICB in patients with solid tumors affording a superior, universal tumor targeting mechanism that bypasses the limitations of ADCs. 1. Gayle S et al. 2021.Tumor-selective, antigen-independent delivery of a pH sensitive peptide-topoisomerase inhibitor conjugate suppresses tumor growth without systemic toxicity. NAR Cancer. 2. Rather than targeting a specific antigen, alphalexTM includes a pHLIP® peptide. pHLIP® peptides are a family of pH-Low Insertion Peptides that target acidic cell surfaces. pHLIP® was developed at Yale University and the University of Rhode Island, and is exclusively licensed to pHLIP, Inc. 3. Wyatt LC et al. 2017. Applications of pHLIP Technology for Cancer Imaging and Therapy. Trends Biotech. 4. Wyatt LC et al. 2018. Peptides of pHLIP family for targeted intracellular and extracellular delivery of cargo molecules to tumors. PNAS. Citation Format: Sophia Gayle, Juan Vasquez, Timothy Paradis, Kelli Jones, Ranjini Sundaram, Jinny van Doorn, Viswanathan Muthusamy, Ranjit S. Bindra, Robert J. Aiello, Vishwas Paralkar. CBX-12 (alphalexTM-exatecan) sensitizes tumors to immune checkpoint blockade in an antigen agnostic manner by immune activation [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P258.

Direct Trocar Insertion: an Efficient Access Technique for Laparoscopic Cholecystectomy

Aim: To evaluate the feasibility and safety of direct trocar insertion for gaining access to peritoneal cavity in laparoscopic cholecystectomy. Methods: An Observational study was conducted at Surgical unit II Ghulam Mohammad Mahar Medical College Hospital Sukkur from January 2016 to December 2020. Two thousand one hundred twenty (n=2120) patients were included in the study. All the patients who underwent laparoscopic cholecystectomy were included in the study. Informed and written consent was obtained from every patient to participate as study subject. Data was analyzed on SPSS version 16. Mean +/- standard deviation was calculated for age, first port access time and time to establish pneumoperitoneum. Results: Under general anesthesia with patient in supine posture, abdominal access gained by first making small incision of 10mm in skin and subcutaneous fat at sub umbilical region with No. 11 scalpel and then by direct trocar insertion followed by creation of pneumoperitoneum. Cholecystectomy performed. Study variables included first port access time, no. of attempts for DTI, extraperitoneal CO2 insufflation, port site bleeding, visceral injury, port site infection and port site hernia and were recorded on predesigned proforma. Variables like extraperitoneal CO2 insufflation, port site bleeding and visceral injury were expressed as percentage. Conclusion: We conclude that direct trocar insertion is the safe, quick and effective method for creation of pneumoperitoneum and should be employed routinely in all laparoscopic procedures. Keywords: Laparoscpy, Cholecystectomy, Trocars

Predicting Winter Wheat Grain Yield Using Fractional Green Canopy Cover (FGCC)

Optical sensors have grown in popularity for estimating plant health, and they form the basis of midseason yield estimations and nitrogen (N) fertilizer recommendations, such as the Oklahoma State University (OSU) nitrogen fertilization optimization algorithm (NFOA). That algorithm uses measurements of normalized difference vegetative index (NDVI), yet not all producers have access to the sensors required to make these measurements. In contrast, most producers have access to smartphones, which can measure fractional green canopy cover (FGCC) using the Canopeo app, but the usefulness of these measurements for midseason yield estimations remains untested. Our objectives were to (1) quantify the relationship between NDVI and FGCC, (2) assess the potential for using FGCC values in place of NDVI values in the current OSU Yield Prediction Model, and (3) compare the performance of NDVI and FGCC-based yield prediction models from the collected dataset. This project, implemented on 13 winter wheat sites over the 2019-2020 growing season, used a range of nitrogen (N) rates (0, 34, 67, 101, and 134 kg N ha−1) to provide different levels of yield. Our results indicated that while NDVI and FGCC are highly correlated (r2 = 0.76), FGCC is not suitable for direct insertion into the current yield prediction model. However, a yield prediction model derived from FGCC provided similar estimates of yield compared to NDVI (Nash Sutcliffe Efficiency = −3.3). This new FGCC-based model will give more producers access to sensor-based yield prediction and N rate recommendations.

Pre-Clinical Development of a Highly Efficient TALEN ®-Based Correction of the β-Globin Gene in Patient-Derived Hematopoietic Stem and Progenitor Cells (HSPCs) to Treat Sickle Cell Disease

Pre-Clinical Development of a Highly Efficient TALEN ®-Based Correction of the β-Globin Gene in Patient-Derived Hematopoietic Stem and Progenitor Cells (HSPCs) to Treat Sickle Cell Disease

Dual-Silicon-Doped Graphitic Carbon Nitride Sheet: An Efficient Metal-Free Electrocatalyst for Urea Synthesis.

Searching for an alternative nonhazardous catalyst for direct urea synthesis that avoids the traditional route of NH3 synthesis followed by CO2 addition is a challenging field of research nowadays. Based on first-principles calculations, we herein propose a novel electrocatalyst comprising of totally nonmetal earth abundant elements (dual-Si doped g-C6N6 sheet) which is capable of activating N2 and making it susceptible toward direct insertion of CO into the N-N bond, producing *NCON* which is the precursor for urea production by direct coupling of N2 and CO2 followed by multiple proton coupled electron transfer processes. Remarkably, the calculated onset potential for urea production is much less than that of NH3 synthesis and hydrogen evolution reactions, and also the faradaic efficiency is nearly 100% for production urea over ammonia, which promotes exclusive electrocatalytic urea synthesis by suppressing the NH3 synthesis as well as hydrogen evolution reactions.

Properties of tissue within prostate tumors and treatment planning implications for ablation therapies.

Irreversible electroporation (IRE) is a promising alternative therapy for the local treatment of prostate tumors. The procedure involves the direct insertion of needle electrodes into the target zone, and subsequent delivery of short but high-voltage pulses. Successful outcomes rely on adequate exposure of the tumor to a threshold electrical field. To aid in predicting this exposure, computational models have been developed, yet often do not incorporate the appropriate tissue-specific properties. This work aims to quantify electrical conductivity behavior during IRE for three types of tissue present in the target area of a prostate cancer ablation: the tumor tissue itself, the surrounding healthy tissue, and potential areas of necrosis within the tumor. Animal tissues were used as a stand-in for primary samples. The patient-derived prostate tumor tissue showed very similar responses to healthy porcine prostate tissue. An examination of necrotic tissue inside the tumors revealed a large difference, however, and a computational model showed that a necrotic core with differing electrical properties can cause unexpected inhomogeneities within the treatment region.

Anterior cruciate ligament reconstruction with femoral direct fiber insertion: a novel technique.

Anterior cruciate ligament reconstruction with femoral direct fiber insertion: a novel technique.

A comparative study between direct safety trocar insertion versus veress needle technique for creating pneumoperitoneum in laparoscopic surgeries

Background: There are two methods of trocar insertion in laparoscopic surgeries one is direct insertion and second is Veress needle insertion. In this study we compared these two methods.Methods: In this study we divided 50 patients equally into two group group A for in group A patients, direct trocar insertion technique was used for creation of pneumoperitoneum whereas amongst patients of group B, pneumoperitoneum was created using Veress needle insertion technique.Results: The incidence of visceral injuries, vascular injuries and other post-operative complications were similar in both the groups. The present study observed no significant difference in failure rates between two methods.Conclusions: Both the techniques i.e.; Direct trocar insertion (DTI) and Veress needle technique are equally effective, safe and feasible for creation of pneumoperitoneum during laparoscopic procedure.

The Stress-Active Cell Division Protein ZapE Alters FtsZ Filament Architecture to Facilitate Division in Escherichia coli.

During pathogenic infections, bacterial cells experience environmental stress conditions, including low oxygen and thermal stress. Bacterial cells proliferate during infection and divide by a mechanism characterized by the assembly of a large cytoskeletal structure at the division site called the Z-ring. The major protein constituting the Z-ring is FtsZ, a tubulin homolog and GTPase that utilizes the nucleotide to assemble into dynamic polymers. In Escherichia coli, many cell division proteins interact with FtsZ and modulate Z-ring assembly, while others direct cell wall insertion and peptidoglycan remodeling. Here, we show that ZapE, an ATPase that accumulates during late constriction, directly interacts with FtsZ and phospholipids in vitro. In the presence of adenosine triphosphate (ATP), ZapE induces bundling of GTP-induced FtsZ polymers; however, ZapE also binds FtsZ in the absence of GTP. The ZapE mutant protein ZapE(K84A), which is defective for ATP hydrolysis, also interacts with FtsZ and induces FtsZ filament bundling. In vivo, cultures of zapE deletion cells contain a low percentage of filamentous cells, suggesting that they have a modest division defect; however, they are able to grow when exposed to stress, such as high temperature and limited oxygen. When combined with the chromosomal deletion of minC, which encodes an FtsZ disassembly factor, ΔzapE ΔminC cells experience growth delays that slow proliferation at high temperature and prevent recovery. This synthetic slow growth phenotype after exposure to stress suggests that ZapE may function to ensure proliferation during and after stress, and this is exacerbated when cells are also deleted for minC. Expression of either ZapE or ZapE(K84A) complements the aberrant growth phenotypes in vivo suggesting that the division-associated role of ZapE does not require ZapE ATP hydrolysis. These results support that ZapE is a stress-regulated cell division protein that interacts directly with FtsZ and phospholipids, promoting growth and division after exposure to environmental stress.

Improving Ensemble Volcanic Ash Forecasts by Direct Insertion of Satellite Data and Ensemble Filtering

Improved quantitative forecasts of volcanic ash are in great demand by the aviation industry to enable better risk management during disruptive volcanic eruption events. However, poor knowledge of volcanic source parameters and other dispersion and transport modelling uncertainties, such as those due to errors in numerical weather prediction fields, make this problem very challenging. Nonetheless, satellite-based algorithms that retrieve ash properties, such as mass load, effective radius, and cloud top height, combined with inverse modelling techniques, such as ensemble filtering, can significantly ameliorate these problems. The satellite-retrieved data can be used to better constrain the volcanic source parameters, but they can also be used to avoid the description of the volcanic source altogether by direct insertion into the forecasting model. In this study we investigate the utility of the direct insertion approach when employed within an ensemble filtering framework. Ensemble members are formed by initializing dispersion models with data from different timesteps, different values of cloud top height, thickness, and NWP ensemble members. This large ensemble is then filtered with respect to observations to produce a refined forecast. We apply this approach to 14 different eruption case studies in the tropical atmosphere. We demonstrate that the direct insertion of data improves model forecast skill, particularly when it is used in a hybrid ensemble in which some ensemble members are initialized from the volcanic source. Moreover, good forecast skill can be obtained even when detailed satellite retrievals are not available, which is frequently the case for volcanic eruptions in the tropics.

Validation Study of a Novel Chest Tube Placement Device: Comparison of Procedure Time and Lung Injury Risk Between the JD Hook® Device and Conventional Chest Tube Placement Devices

Background: We tested the operational characteristics of JD Hook ® prototype device and compared it to currently available direct chest tube insertion (non-Seldinger) devices in terms of procedure time, safety and risk of lung injury. Methods: Two commercially chest tube devices including a 28 Fr chest tube with trocars, a 24 Fr chest tube with a Kelly forceps clamp and JD Hook ® prototype pleural access device were tested on standard thoracic manikin, for comparative procedure time and risk of lung injury. Results: JD Hook ® pleural access device showed the shortest procedure time with least risk of lung injury compared to conventional access devices. Both results were statistically significant. Conclusions: JD Hook ® device is a safer and faster access device compared to conventional chest tube access devices. Additional studies in animal and cadavers models are needed to validate these results for clinical applications. J Curr Surg. 2021;11(3):51-56 doi: https://doi.org/10.14740/jcs447

Visible Light-Driven CO2 Insertion on Phenylacetylene to Phenylpropiolic Acid Using Soft-Oxometalates

The visible light-driven CO2 insertion from phenylacetylene to acetophenone using soft-oxometalates (SOMs) as a photocatalyst is an important step in the pursuit of C–H activation. We have demonstrated a synergistic combination of Cu-based SOMs and Cs2CO3 at ambient pressure and temperature to lower the activation energy barrier for CO2 insertion. The water in the medium acts as a source of proton and the reaction is driven by Cu(II)/Cu(I) couple. The reaction yields a good amount of phenylpropiolic acid under mild condition. We further believe this work could open up a new avenue for direct CO2 insertion under mild condition.

Extension Block Pinning versus percutaneous Fragment Reduction with a Towel Clip and extension Block Pinning with direct Pin Fixation for Treatment of Mallet Fracture.

This study compared the clinical and radiographic results between extension block pinning (Group A) and percutaneous reduction of the dorsal fragment with a towel clip followed by extension block pinning with direct pin fixation (Group B) for the treatment of mallet fractures. A total of 69 patients (group A = 34 patients, group B = 35 patients) who underwent operative treatment for mallet fractures from June 2008 to November 2017 with ≥ 6 months post-surgical follow-up were analysed retrospectively. The extent of subluxation of the distal interphalangeal joint, articular involvement of fracture fragment, fracture gap, and articular step-off were examined on plain radiographs before and after surgery. The functional outcomes were evaluated with the Crawford rating system. The postoperative step-offs were 0.16 mm in group A and 0.01 mm in group B. Group B had a significantly better anatomical outcome than group A. Five patients in group A had a loss of reduction. Among them, two had malunion and post-traumatic arthritis. Meanwhile, no patients in group B presented with loss of reduction and nonunion. The mean extension lags were 4.2° in group A and 1.6° in group B. However, functional outcome did not differ between the two groups at the final follow-up. Fracture reduction using a towel clip and extension block pinning with direct pin insertion for mallet fracture facilitated the anatomical reduction of fragments, and allowed for stable fixation of fragments. Compared with extension block pinning technique, this technique has shown better anatomical results and stability, but not better clinical results.

Failure load of the femoral insertion site of the anterior cruciate ligament in a porcine model: comparison of different portions and knee flexion angles

BackgroundThis study compared the failure load of the femoral insertion site of the anterior cruciate ligament between different portions and knee flexion angles.MethodsIn total, 87 fresh-frozen, porcine knees were used in this study. Three knees were used for histological evaluation; the remaining 84 knees were randomly divided into 4 groups: anterior anteromedial bundle, posterior anteromedial bundle, anterior posterolateral bundle, and posterior posterolateral bundle groups (n=21 per group). The anterior cruciate ligament femoral insertion site was divided into these four areas and excised, leaving a 3-mm square attachment in the center of each bundle. Tibia-anterior cruciate ligament-femur complexes were placed in a material testing machine at 30°, 120°, and 150° of knee flexion (n=7), and the failure load for each portion was measured under anterior tibial loading (0.33 mm/s).ResultsHistological study showed that the anterior cruciate ligament femoral insertion site consisted of direct and indirect insertions. Comparison of the failure load between the knee flexion angles revealed that all the failure loads decreased with knee flexion; significant decreases were observed in the failure load between 30 and 150° knee flexion in the posterior anteromedial bundle and posterior posterolateral bundle groups. Comparison of the failure load according to different portions revealed a significant difference between the anteromedial and posterolateral bundle groups at 150° of knee flexion, but no significant difference among the groups at 30° of flexion.ConclusionsAlthough the failure load of the posterior portion decreased significantly in the knee flexion position, it (mainly consisting of indirect insertion) plays a significant role against anterior tibial load in the knee extension position; this appears to be related to the characteristics of the insertion site. Reflecting the complex structure and function of the ACL, this study showed that the failure load of the femoral insertion site varies with differences in positions and knee flexion angles.

Accuracy of direct insertion of TADs in the anterior palate with respect to a 3D-assisted digital insertion virtual planning.

Direct and 3D-assisted methods are an available alternative when inserting temporary anchorage devices (TADs) in the anterior palate for orthodontic anchorage. This study aimed to evaluate the differences between a planned insertion versus a direct method on digital models. Seventy TADs were inserted by the direct insertion method in 35 patients who needed palatal TADs for orthodontic anchorage. For each patient, placement was independently planned by the superimposition of lateral cephalograms and corresponding plaster models. After mini-implant placement, impressions were taken with scanbodies. For the measurement of both linear and angle deviations, virtual planning models and postoperative oral scans were compared using 3D software for automatic surface registration and calculations. Comparing TADs positioned by the direct method and the digitally planned method, a mean linear distance was found of 2.54±1.51mm in the occlusal view and 2.41±1.33mm in the sagittal view. No significant difference has been found between TADs positioned in the right and left palatal sides. A mean distance of 7.65±2.16mm was found between the tip of the digitally planned TAD and the central incisors root apex. Both direct and 3D-assisted TAD insertion methods are safe and accurate in the anterior palate. However, the use of insertion guides facilitates TAD insertion, allowing less-experienced clinicians to use palatal implants.

Comparison of Complications between Direct Trocar Insertion Versus Veress Needle for Creation of Pneumoperitoneum in Patients Undergoing laparoscopic Cholecystectomy: A Randomized Control Trial

Aim: To compare the outcomes in term of complication of Veress Needle Insertion (VNI) to Direct Trocar Insertion (DTI) for creation of pneumoperitoneum in laparoscopic cholecystectomy.
 Design: Randomized controlled trial
 Place and Duration of Study: The current analysis was conducted at Khawaja Muhammad Safdar Medical College Surgical Department, Allama Iqbal Memorial Hospital and Govt. Sardar Begum Teaching Hospital, Sialkot from September 27, 2017, to September 26, 2020.
 Methodology: A total of six hundred and eight (n=608) patients, having age 30 to 75 years planned for laparoscopic cholecystectomy were included in this study. Patients were randomly divided into two groups, Group A (Direct Trocar Insertion), Group B (Veress Needle Insertion). Both groups had age and sex matched males and female. All trocars and veress needle used were disposable, with a safety shield. The primary outcome of our study was to compare the complications to assess the safety levels, while total time taken by the procedure and mean time for laparoscopic entry were the secondary end points. The collected data was analyzed by using software SPSS version 22. Chi-square test was used to check the significance of variance. P-value less than 0.05 remained the statistically significant.
 Results: The complication rate in VNI group were significantly greater than the DTI group (p < 0.01), the duration of surgery between the two groups was not significantly different (p > 0.05), but we found statistically significant difference in mean laparoscope insertion time (DTI 3.4+ 1.4 versus VNI 4.8+ 0.7 minutes, p < 0.001).
 Conclusion: From the results of our study, it can be concluded that the direct trocar insertion is a safe alternative to veress needle insertion in laparoscopic cholecystectomy as it is associated with fewer complications.