Machine Learning-Guided Prediction of Antigen-Reactive In Silico Clonotypes Based on Changes in Clonal Abundance through Bio-Panning.

c-Met is a promising target in cancer therapy for its intrinsic oncogenic properties. However, there are currently no c-Met-specific inhibitors available in the clinic. Antibodies blocking the interaction with its only known ligand, hepatocyte growth factor, and/or inducing receptor internalization have been clinically tested. To explore other therapeutic antibody mechanisms like Fc-mediated effector function, bispecific T cell engagement, and chimeric antigen T cell receptors, a diverse panel of antibodies is essential. We prepared a chicken immune scFv library, performed four rounds of bio-panning, obtained 641 clones using a high-throughput clonal retrieval system (TrueRepertoireTM, TR), and found 149 antigen-reactive scFv clones. We also prepared phagemid DNA before the start of bio-panning (round 0) and, after each round of bio-panning (round 1-4), performed next-generation sequencing of these five sets of phagemid DNA, and identified 860,207 HCDR3 clonotypes and 443,292 LCDR3 clonotypes along with their clonal abundance data. We then established a TR data set consisting of antigen reactivity for scFv clones found in TR analysis and the clonal abundance of their HCDR3 and LCDR3 clonotypes in five sets of phagemid DNA. Using the TR data set, a random forest machine learning algorithm was trained to predict the binding properties of in silico HCDR3 and LCDR3 clonotypes. Subsequently, we synthesized 40 HCDR3 and 40 LCDR3 clonotypes predicted to be antigen reactive (AR) and constructed a phage-displayed scFv library called the AR library. In parallel, we also prepared an antigen non-reactive (NR) library using 10 HCDR3 and 10 LCDR3 clonotypes predicted to be NR. After a single round of bio-panning, we screened 96 randomly-selected phage clones from the AR library and found out 14 AR scFv clones consisting of 5 HCDR3 and 11 LCDR3 AR clonotypes. We also screened 96 randomly-selected phage clones from the NR library, but did not identify any AR clones. In summary, machine learning algorithms can provide a method for identifying AR antibodies, which allows for the characterization of diverse antibody libraries inaccessible by traditional methods.

The composite anterolateral thigh flap for knee extensor and skin reconstruction.

The simultaneous reconstruction of a skin defect and lost extensor mechanism of the knee joint is difficult. We present a 31-year-old male who lost the patella and had a 9 × 10 cm skin defect after a total patellectomy for an infected open patellar fracture. A composite anterolateral thigh (ALT) flap including vascularized skin and fascia lata (FL) was elevated. The FL was folded and sutured to the remaining patellar tendon. The skin flap covered the skin defect. The wound healed uneventfully. Thirty months later, the active range of motion of the knee joint was 0°-120° and the extension strength of the knee joint was normal. He could stand on his right leg and walk without assistance. The composite ALT flap is a valuable option in knee reconstruction after a total patellectomy.

Physical electro-thermal model of resistive switching in bi-layered resistance-change memory.

Tantalum-oxide-based bi-layered resistance-change memories (RRAMs) have recently improved greatly with regard to their memory performances. The formation and rupture of conductive filaments is generally known to be the mechanism that underlies resistive switching. The nature of the filament has been studied intensively and several phenomenological models have consistently predicted the resistance-change behavior. However, a physics-based model that describes a complete bi-layered RRAM structure has not yet been demonstrated. Here, a complete electro-thermal resistive switching model based on the finite element method is proposed. The migration of oxygen vacancies is simulated by the local temperature and electric field derived from carrier continuity and heat equations fully coupled in a 3-D geometry, which considers a complete bi-layered structure that includes the top and bottom electrodes. The proposed model accurately accounts for the set/reset characteristics, which provides an in-depth understanding of the nature of resistive switching.

Modeling for multilevel switching in oxide-based bipolar resistive memory.

We report a physical model for multilevel switching in oxide-based bipolar resistive memory (ReRAM). To confirm the validity of the model, we conduct experiments with tantalum-oxide-based ReRAM of which multi-resistance levels are obtained by reset voltage modifications. It is also noticeable that, in addition to multilevel switching capability, the ReRAM exhibits extremely different switching timescales, i.e. of the order of 10(-7) s to 10(0) s, with regard to reset voltages of only a few volts difference which can be well explained by our model. It is demonstrated that with this simple model, multilevel switching behavior in oxide bipolar ReRAM can be described not only qualitatively but also quantitatively.

Myotonic dystrophy type 1 presenting as male infertility.

Myotonic dystrophy 1 (DM1) is a multi-system disorder characterized by endocrine defects that include testicular and tubular atrophy, oligospermia and azoospermia, and increased follicle-stimulating hormone levels. We describe a rare case of DM1 presenting as infertility in a 29-year-old man.

A fast, high-endurance and scalable non-volatile memory device made from asymmetric Ta2O(5-x)/TaO(2-x) bilayer structures.

Numerous candidates attempting to replace Si-based flash memory have failed for a variety of reasons over the years. Oxide-based resistance memory and the related memristor have succeeded in surpassing the specifications for a number of device requirements. However, a material or device structure that satisfies high-density, switching-speed, endurance, retention and most importantly power-consumption criteria has yet to be announced. In this work we demonstrate a TaO(x)-based asymmetric passive switching device with which we were able to localize resistance switching and satisfy all aforementioned requirements. In particular, the reduction of switching current drastically reduces power consumption and results in extreme cycling endurances of over 10(12). Along with the 10 ns switching times, this allows for possible applications to the working-memory space as well. Furthermore, by combining two such devices each with an intrinsic Schottky barrier we eliminate any need for a discrete transistor or diode in solving issues of stray leakage current paths in high-density crossbar arrays.

Mucoepidermoid carcinoma of the lacrimal sac after dacryocystectomy for squamous papilloma.

A mass that recurred after dacryocystectomy for benign squamous papilloma of the lacrimal sac was diagnosed as a high-grade mucoepidermoid carcinoma in a 53-year-old man on histopathology. Local excision to the orbital periosteum was performed and gave a margin free of invasion. Neither local recurrence nor systemic metastasis was found 3 years after local excision. Mucoepidermoid carcinoma of the lacrimal sac is extremely rare and spreads locally in an aggressive manner; a cure typically requires exenteration, radical resection, or adjuvant radiotherapy. In this rare case, despite the high malignancy, the patient underwent successful local excision, achieved an aesthetically satisfying result, and has had a long-term cancer-free period.

Trifurcated radial nerve in the spiral groove of the humerus.

A 62-year-old man presented with a nonunion of the humerus shaft. Using a standard triceps splitting approach, a longitudinal incision along the posterior aspect of the arm was created. Three independent radial nerves coursed posteriorly and inferolaterally around the humerus were identified in spiral groove. Three nerves resembled in the size, color, and course in the operative field. Although the prevalence of the anomaly is probably quite low, the possibility of identification of this anomalous condition of radial nerve should be kept in mind when performing posterior approach on the humerus.

Percutaneous temporal wiring method for minimally invasive plate osteosynthesis of distal femoral fractures.

The surgical reduction of distal femoral fractures with minimally invasive plate osteosynthesis is difficult and the maintenance of the reduction can involve high exposures to radiation. We designed an effective fracture reduction method involving a percutaneous temporal wiring technique for the reduction of distal femoral fractures with oblique or spiral fracture components during surgery with minimally invasive plate osteosynthesis. Our method consistently reduced these fractures satisfactorily. The maintenance of reduction and plate fixation were easy with our method and the radiation exposure during the operation was reduced.