An Achievability Scheme for the Compound Channel with State Noncausally Available at the Encoder

A new achievability scheme for the compound channel with discrete memoryless (DM) state noncausally available at the encoder is established. Achievability is proved using superposition coding, Marton coding, joint typicality encoding, and indirect decoding. The scheme is shown to achieve strictly higher rate than the straightforward extension of the Gelfand-Pinsker coding scheme for a single DMC with DM state, and is optimal for some classes of channels.Comment: 11 page

1-(5-Bromo-4-phenyl-1,3-thia­zol-2-yl)pyrrolidin-2-one

The asymmetric unit of the title compound, C13H11BrN2OS, consists of two crystallographically independent mol­ecules (A and B). In each mol­ecule, the pyrrolidine ring adopts an envelope conformation with a methyl­ene C atom as the flap atom. In mol­ecule A, the central thia­zole ring makes a dihedral angle of 36.69 (11)° with the adjacent phenyl ring, whereas the corresponding angle is 36.85 (12)° in mol­ecule B. The pyrrolidine ring is slightly twisted from the thia­zole ring, with C—N—C—N torsion angles of 4.8 (3) and 3.0 (4)° in mol­ecules A and B, respectively. In the crystal, C—H⋯π and π–π [centroid-to-centroid distance = 3.7539 (14) Å] inter­actions are observed. The crystal studied was a pseudo-merohedral twin with twin law (-100 0-10 101) and a refined component ratio of 0.7188 (5):0.2812 (5)

An Open-Label, Multicenter, Phase I, Dose Escalation Study with Phase II Expansion Cohort to Determine the Safety, Pharmacokinetics, and Preliminary Antitumor Activity of Intravenous TKM-080301 in Subjects with Advanced Hepatocellular Carcinoma.

Lessons learnedTKM-080301 showed a favorable toxicity profile at the studied dose.TKM-080301 targeting PLK1 through small interfering RNA mechanism did not demonstrate improved overall survival in patients with advanced hepatocellular carcinoma compared with historical control. Preliminary antitumor activity as shown in this early-phase study does not support further evaluation as a single agent.BackgroundPolo-like kinase 1 (PLK1) is overexpressed in hepatocellular carcinoma (HCC). Knockdown of PLK1 expression by PLK1 small interfering RNA (siRNA) in an HCC cell line showed reduced expression in RNA-induced silencing complex and a reduction in cell proliferation.MethodsA 3 + 3 dose escalation plus expansion cohort at the maximum tolerated dose (MTD) was implemented. Patients with HCC, Eastern Cooperative Oncology Group (ECOG) performance status ≤2, and Child-Pugh score A received TKM-080301 as an intravenous infusion once every week for 3 consecutive weeks, repeated every 28 days.ResultsThe study enrolled 43 patients. The starting dose of TKM-080301 was 0.3 mg/kg, and MTD was declared at 0.75 mg/kg. Following the development of grade 4 thrombocytopenia in two subjects on the expansion cohort, the MTD was redefined at 0.6 mg/kg. Four patients did not have any evaluable postbaseline scan. Of the other 39 subjects who had received at least 0.3 mg/kg, 18 subjects (46.2%) had stable disease (SD) by independent RECIST 1.1 criteria. By Choi criteria, eight subjects (23.1%) had a partial response (PR). For 37 assessable subjects, with 2 subjects censored, median progression-free survival (PFS) was 2.04 months. Median survival for the whole study population was 7.5 months.ConclusionTKM-080301 was generally well tolerated. In this early-phase study, antitumor effect for TKM 080301 was limited. Further evaluation as a single agent in large randomized trials is not warranted

Ethyl 2-amino-4-(4-fluoro­phen­yl)-6-meth­oxy-4H-benzo[h]chromene-3-carboxyl­ate

In the title compound, C23H20FNO4, the fluoro-substituted benzene ring is approximately perpendicular to the mean plane of the 4H-benzo[h]chromene ring system [maximum deviation = 0.264 (1) Å], with a dihedral angle of 83.79 (6)°. The pyran ring adopts a flattened boat conformation. The meth­oxy group is slightly twisted from the attached benzene ring of the 4H-benzo[h]chromene moiety [C—O—C—C = −2.1 (2)°]. An intra­molecular N—H⋯O hydrogen bond generates an S(6) ring motif. In the crystal, mol­ecules are linked by N—H⋯O and N—H⋯F hydrogen bonds into a layer parallel to the bc plane. The crystal packing also features C—H⋯π inter­actions

3-[(N-Methyl­anilino)meth­yl]-5-(thio­phen-2-yl)-1,3,4-oxadiazole-2(3H)-thione

In the title compound, C14H13N3OS2, the thio­phene ring is disordered over two orientations by ca 180° about the C—C bond axis linking the ring to the rest of the mol­ecule, with a site-occupancy ratio of 0.651 (5):0.349 (5). The central 1,3,4-oxadiazole-2(3H)-thione ring forms dihedral angles of 9.2 (5), 4.6 (11) and 47.70 (7)° with the major and minor parts of the disordered thio­phene ring and the terminal phenyl ring, respectively. In the crystal, no significant inter­molecular hydrogen bonds are observed. The crystal packing is stabilized by π–π inter­actions [centroid–centroid distance = 3.589 (2) Å]

Capabilities of GPT-4 in ophthalmology: an analysis of model entropy and progress towards human-level medical question answering

Background: Evidence on the performance of Generative Pre-trained Transformer 4 (GPT-4), a large language model (LLM), in the ophthalmology question-answering domain is needed. // Methods: We tested GPT-4 on two 260-question multiple choice question sets from the Basic and Clinical Science Course (BCSC) Self-Assessment Program and the OphthoQuestions question banks. We compared the accuracy of GPT-4 models with varying temperatures (creativity setting) and evaluated their responses in a subset of questions. We also compared the best-performing GPT-4 model to GPT-3.5 and to historical human performance. // Results: GPT-4–0.3 (GPT-4 with a temperature of 0.3) achieved the highest accuracy among GPT-4 models, with 75.8% on the BCSC set and 70.0% on the OphthoQuestions set. The combined accuracy was 72.9%, which represents an 18.3% raw improvement in accuracy compared with GPT-3.5 (p<0.001). Human graders preferred responses from models with a temperature higher than 0 (more creative). Exam section, question difficulty and cognitive level were all predictive of GPT-4-0.3 answer accuracy. GPT-4-0.3’s performance was numerically superior to human performance on the BCSC (75.8% vs 73.3%) and OphthoQuestions (70.0% vs 63.0%), but the difference was not statistically significant (p=0.55 and p=0.09). // Conclusion: GPT-4, an LLM trained on non-ophthalmology-specific data, performs significantly better than its predecessor on simulated ophthalmology board-style exams. Remarkably, its performance tended to be superior to historical human performance, but that difference was not statistically significant in our study