This dissertation studies TFNP, the class of total NP search problems, and TFNP², a relativized version of TFNP. Resolving the exact computational complexities of TFNP and its subclasses is closely tied to the P versus NP question, thus the main focus is on the relativized class TFNP². The subclasses of TFNP² which we study are "syntactic", meaning that their totality is guaranteed by some combinatorial lemma. A main result is that there is a strong connection between TFNP² and propositional proofs. We show that a Turing reduction from Q₁ to Q₂ gives rise to constant depth, polynomial size propositional (Frege) proofs between the underlying combinatorial lemmas. We show that a similar result holds for polylogarithmic degree Nullstellensatz refutations. These results were shown only for the many-one case in [9]. These new translations provide new Turing separations by using existing upper and lower bounds from proof complexity. We also solve an open problem stated in [9] by showing that a reverse construction also holds. Namely, we prove that constant depth, polynomial size propositional proofs of the totality of one combinatorial lemma from another combinatorial lemma give rise to a Turing reduction between the corresponding TFNP² problems. Another point of investigation is the relation between many-one and Turing reducibility. We show that for many natural TFNP² classes many-one and Turing reducibility are equivalent. To show that this result does not hold in general, we construct a TFNP² problem whose Turing closure is strictly larger than its many-one closure. To generalize these results, we introduce a new type of reducibility called k-reducibility, and show that k- and (k + 1)-reducibility are not equivalent. This last result makes use of modular counting principles. These have been previously studied as propositional formulas, but we introduce them as TFNP² problems called MODd. We prove results about the relative complexity of the MODd's between themselves and other interesting TFNP² classes. By constructing equivalences between the propositional translation of MODd and the modular counting principles of [3], we can use the provability results in [3] to prove separations

Electronic DNA-biosensor with a single nucleotide resolution capability is highly desirable for personalized medicine. However, existing DNA-biosensors, especially single nucleotide polymorphism (SNP) detection systems, have poor sensitivity and specificity and lack real-time wireless data transmission. DNA-tweezers with graphene field effect transistor (FET) are used for SNP detection and data are transmitted wirelessly for analysis. Picomolar sensitivity of quantitative SNP detection is achieved by observing changes in Dirac point shift and resistance change. The use of DNA-tweezers probe with high-quality graphene FET significantly improves analytical characteristics of SNP detection by enhancing the sensitivity more than 1000-fold in comparison to previous work. The electrical signal resulting from resistance changes triggered by DNA strand-displacement and related changes in the DNA geometry is recorded and transmitted remotely to personal electronics. Practical implementation of this enabling technology will provide cheaper, faster, and portable point-of-care molecular health status monitoring and diagnostic devices.

Electronic DNA-biosensor with a single nucleotide resolution capability is highly desirable for personalized medicine. However, existing DNA-biosensors, especially single nucleotide polymorphism (SNP) detection systems, have poor sensitivity and specificity and lack real-time wireless data transmission. DNA-tweezers with graphene field effect transistor (FET) are used for SNP detection and data are transmitted wirelessly for analysis. Picomolar sensitivity of quantitative SNP detection is achieved by observing changes in Dirac point shift and resistance change. The use of DNA-tweezers probe with high-quality graphene FET significantly improves analytical characteristics of SNP detection by enhancing the sensitivity more than 1000-fold in comparison to previous work. The electrical signal resulting from resistance changes triggered by DNA strand-displacement and related changes in the DNA geometry is recorded and transmitted remotely to personal electronics. Practical implementation of this enabling technology will provide cheaper, faster, and portable point-of-care molecular health status monitoring and diagnostic devices.

OBJECTIVE: To review new drugs and devices relevant to otolaryngology approved by the Food and Drug Administration (FDA) in 2022. DATA SOURCES: Publicly available FDA data on drugs and devices approved in 2022. REVIEW METHODS: A preliminary screen was conducted to identify drugs and devices relevant to otolaryngology. A secondary screen by members of the American Academy of Otolaryngology-Head and Neck Surgerys (AAO-HNS) Medical Devices and Drugs Committee differentiated between minor updates and new approvals. The final list of drugs and devices was sent to members of each subspecialty for review and analysis. CONCLUSION: A total of 1251 devices and 37 drugs were identified on preliminary screening. Of these, 329 devices and 5 drugs were sent to subspecialists for further review, from which 37 devices and 2 novel drugs were selected for further analysis. The newly approved devices spanned all subspecialties within otolaryngology. Many of the newly approved devices aimed to enhance patient experience, including over-the-counter hearing aids, sleep monitoring devices, and refined CPAP devices. Other advances aimed to improve surgical access, convenience, or comfort in the operating room and clinic. IMPLICATIONS FOR PRACTICE: Many new devices and drugs are approved each year to improve patient care and care delivery. By staying up to date with these advances, otolaryngologists can leverage new innovations to improve the safety and quality of care. Given the recent approval of these devices, further studies are needed to assess long-term impact within the field of otolaryngology.