PoET: A generative model of protein families as sequences-of-sequences

Generative protein language models are a natural way to design new proteins with desired functions. However, current models are either difficult to direct to produce a protein from a specific family of interest, or must be trained on a large multiple sequence alignment (MSA) from the specific family of interest, making them unable to benefit from transfer learning across families. To address this, we propose $\textbf{P}$r$\textbf{o}$tein $\textbf{E}$volutionary $\textbf{T}$ransformer (PoET), an autoregressive generative model of whole protein families that learns to generate sets of related proteins as sequences-of-sequences across tens of millions of natural protein sequence clusters. PoET can be used as a retrieval-augmented language model to generate and score arbitrary modifications conditioned on any protein family of interest, and can extrapolate from short context lengths to generalize well even for small families. This is enabled by a unique Transformer layer; we model tokens sequentially within sequences while attending between sequences order invariantly, allowing PoET to scale to context lengths beyond those used during training. In extensive experiments on deep mutational scanning datasets, we show that PoET outperforms existing protein language models and evolutionary sequence models for variant function prediction across proteins of all MSA depths. We also demonstrate PoET's ability to controllably generate new protein sequences

Sentinel surveillance of HIV-1 transmitted drug resistance, acute infection and recent infection.

BackgroundHIV-1 acute infection, recent infection and transmitted drug resistance screening was integrated into voluntary HIV counseling and testing (VCT) services to enhance the existing surveillance program in San Francisco. This study describes newly-diagnosed HIV cases and characterizes correlates associated with infection.Methodology/principal findingsA consecutive sample of persons presenting for HIV VCT at the municipal sexually transmitted infections (STI) clinic from 2004 to 2006 (N = 9,868) were evaluated by standard enzyme-linked immunoassays (EIA). HIV antibody-positive specimens were characterized as recent infections using a less-sensitive EIA. HIV-RNA pooled testing was performed on HIV antibody-negative specimens to identify acute infections. HIV antibody-positive and acute infection specimens were evaluated for drug resistance by sequence analysis. Multivariable logistic regression was performed to evaluate associations. The 380 newly-diagnosed HIV cases included 29 acute infections, 128 recent infections, and 47 drug-resistant cases, with no significant increases or decreases in prevalence over the three years studied. HIV-1 transmitted drug resistance prevalence was 11.0% in 2004, 13.4% in 2005 and 14.9% in 2006 (p = 0.36). Resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI) was the most common pattern detected, present in 28 cases of resistance (59.6%). Among MSM, recent infection was associated with amphetamine use (AOR = 2.67; p<0.001), unprotected anal intercourse (AOR = 2.27; p<0.001), sex with a known HIV-infected partner (AOR = 1.64; p = 0.02), and history of gonorrhea (AOR = 1.62; p = 0.03).ConclusionsNew HIV diagnoses, recent infections, acute infections and transmitted drug resistance prevalence remained stable between 2004 and 2006. Resistance to NNRTI comprised more than half of the drug-resistant cases, a worrisome finding given its role as the backbone of first-line antiretroviral therapy in San Francisco as well as worldwide. The integration of HIV-1 drug resistance, recent infection, and acute infection testing should be considered for existing HIV/STI surveillance and prevention activities, particularly in an era of enhanced efforts for early diagnosis and treatment

SAMS Acceleration Measurement on Mir From March to September 1996

During NASA Increment 2 (March to September 1996), over 15 gigabytes of acceleration data were collected by the Space Acceleration Measurement System (SAMS) onboard the Russian Space Station, Mir. The data were recorded on 55 optical disks and were returned to Earth on STS-79. During this time, SAMS data were collected in the Kristall and Kvant modules, and in the Priroda module to support the following experiments: the Queen's University Experiments in Liquid Diffusion (QUELD), the Technological Evaluation of the MIM (TEM), the Forced Flow Flame Spreading Test (FFFT), and Candle Flames in Microgravity (CFM). This report points out some of the salient features of the microgravity environment to which these experiments were exposed. Also documented are mission events of interest such as the docked phase of STS-76 operations, an extravehicular activity (EVA) to install and deploy solar panels on the Kvant module, a Progress engine burn to raise Mir's altitude, and an on-orbit SAMS calibration procedure. Also included are a description of the Mir module orientations, and the panel notations within the modules. This report presents an overview of the SAMS acceleration measurements recorded by 10 Hz and 100 Hz sensor heads. Variations in the acceleration environment caused by unique activities such as crew exercise and life-support fans are presented. The analyses included herein complement those presented in previous mission summary reports published by the Principal Investigator Microgravity Services (PIMS) group

If you build it, they may not come: Why Australian university students do not take part in outbound mobility experiences.

Universities around the world seek to internalise students to prepare them for an increasingly globalised world. Outbound mobility experiences (OMEs) are recognised as one of the most effective ways to foster independent thinking, cultural sensitivity, and a sense of 'worldmindedness'. This article takes a case study from an Australian university and explores efforts to increase student participation rates in OMEs

LED down the rabbit hole: exploring the potential of global attention for biomedical multi-document summarisation

In this paper we report on our submission to the Multidocument Summarisation for Literature Review (MSLR) shared task. Specifically, we adapt PRIMERA (Xiao et al., 2022) to the biomedical domain by placing global attention on important biomedical entities in several ways. We analyse the outputs of the 23 resulting models, and report patterns in the results related to the presence of additional global attention, number of training steps, and the input configuration.Comment: SDP Workshop at COLING 202

Mixed Goblet Cell Carcinoid-Adenocarcinoma: A Case Series

INTRODUCTION: Mixed goblet cell carcinoid-adenocarcinoma (GCC) tumors are a group of rare heterogenous neoplasms of the appendix accounting for \u3c 5% of all primary appendiceal tumors. They are characterized as an intermediate between classic carcinoid tumors and appendiceal adenocarcinomas, exhibiting both neuroendocrine and glandular/mucinous morphology that most commonly presents in Caucasian females in the fifth and sixth decades. We present three cases of mixed GCC presenting as acute appendicitis. CASE PRESENTATION: Case #1 A 65-year-old male presented with RLQ pain, nausea, emesis, and leukocytosis. CT of the abdomen revealed perforated appendicitis. The patient underwent a laparoscopic appendectomy. Pathology revealed a high-grade adenocarcinoma ex goblet cell carcinoid, signet ring type extending through the muscularis propria into the mesoappendix measuring \u3e3cm. The patient subsequently underwent a colonoscopy that revealed diverticulosis, but was otherwise normal. Patient then underwent a right hemicolectomy and partial omentectomy. Pathology revealed normal ileal, omental, and colonic tissue without evidence of carcinoma. 0/12 nodes were positive. Case #2 A 49-year-old male presented with periumbilical pain, nausea, emesis, and leukocytosis. CT of the abdomen revealed appendicitis. The patient underwent a laparoscopic appendectomy. Pathology revealed a high-grade, poorly differentiated, adenocarcinoma ex goblet cell carcinoid invading through the muscularis propria into the periappendiceal soft tissue measuring 1.5cm. The patient subsequently underwent a colonoscopy that revealed diverticulosis, but was otherwise normal. Patient then underwent a laparoscopic right hemicolectomy. Pathology revealed normal ileal and colonic mucosa without evidence of carcinoma. 0/14 nodes were positive. Case #3 A 70-year-old female presented with periumbilical pain. CT of the abdomen revealed appendicitis. The patient underwent a laparoscopic appendectomy. Pathology revealed a high-grade adenocarcinoma ex goblet cell carcinoid extending through the muscularis propria into the mesoappendix measuring 4cm. Patient then underwent an exploratory laparotomy with a right hemicolectomy. Pathology revealed normal ileal and colonic mucosa without evidence of carcinoma. 0/21 nodes were positive. CONCLUSION: Mixed GCC tumors are rare tumors that tend to present at an advanced stage and most commonly spread via direct extension. Surgical resection with a right hemi-colectomy after an appendectomy has been shown to improve the prognosis. HIPEC and adjuvant chemotherapy are other therapeutic options, but have not been shown to improve survival. In the current age of increasing rates of managing acute appendicitis non-operatively we strongly encourage surgical appendectomy in patients older than 45 years of age to avoid missing this important diagnosis and the opportunity to treat it in a timely manner

Jafari and Transformation: A Model to enhance short-term overseas study tours

This paper promotes a reconstructed Jafari (1987) tourism model as a framework to understand the various components of the student and staff travel experience while participating in an outbound mobility experience (OME), especially short-term overseas study trips. Working through each of the components of the Jafari model allows recognition of the changing needs and requirements of both students and staff throughout an OME and the tensions that accompany this relationship