Miracle-dz/UniFAR-FTUs huggingface dataset:
Modeling Combination Chemo-Immunotherapy for Heterogeneous Tumors

Hypermutable cancers create opportunities for the development of various immunotherapies, such as immune checkpoint blockade (ICB) therapy. However, emergent studies have revealed that many hypermutated tumors have poor prognosis due to heterogeneous tumor antigen landscapes, yet the underlying mechanisms remain poorly understood. To address this issue, we developed mathematical models to explore the impact of combining chemotherapy and ICB therapy on heterogeneous tumors. Our results uncover how chemotherapy reduces antigenic heterogeneity, creating improved immunological conditions within tumors, which, in turn, enhances the therapeutic effect when combined with ICB. Furthermore, our results show that the recovery of the immune system after chemotherapy is crucial for enhancing the response to chemo-ICB combination therapy. Author summary The challenge posed by intratumoral heterogeneity is gaining recognition in the field of cancer treatment. Despite the success of immune checkpoint blockade (ICB) therapies in enhancing overall survival across various cancer types, the complexity of therapeutic responses persists due to the heterogeneity of tumor antigens. In this study, we developed mathematical models to explore the evolutionary dynamics of tumors with both homogeneous and heterogeneous antigen landscapes. Our analysis reveals that tumors with heterogeneity exhibit resistance to ICB therapy, unlike their homogeneous counterparts which respond positively. Additionally, our models demonstrate that early treatment of heterogeneous tumors with chemotherapy leads to significant remission but also rapid recurrence. Notably, we identified a fascinating trade-off associated with chemotherapy—while suppressing the immune system, it creates a tumor immunological environment that becomes more conducive to ICB therapy. Finally, our modeling highlights the augmented response observed in tumors subjected to a chemo-ICB combination and shows the crucial role of immune recovery in the context of combination therapy.
Target-aware Molecule Generation for Drug Design Using a Chemical Language Model*

Generative drug design facilitates the creation of compounds effective against pathogenic target proteins. This opens up the potential to discover novel compounds within the vast chemical space and fosters the development of innovative therapeutic strategies. However, the practicality of generated molecules is often limited, as many designs focus on a narrow set of drug-related properties, failing to improve the success rate of subsequent drug discovery process. To overcome these challenges, we develop TamGen, a method that employs a GPT-like chemical language model and enables target-aware molecule generation and compound refinement. We demonstrate that the compounds generated by TamGen have improved molecular quality and viability. Additionally, we have integrated TamGen into a drug discovery pipeline and identified 7 compounds showing compelling inhibitory activity against the Tuberculosis ClpP protease, with the most effective compound exhibiting a half maximal inhibitory concentration (IC50) of 1.9 μM. Our findings underscore the practical potential and real-world applicability of generative drug design approaches, paving the way for future advancements in the field.
Synopsis of the remarkable family Phloeidae (Hemiptera: Pentatomoidea): species identification, chromatic polymorphism and updated distribution

ABSTRACT The Neotropical family Phloeidae includes three species within two genera, Phloea Lepeletier and Serville, 1825 and Phloeophana Kirkaldy, 1908, distributed in South America. Due to their large size and notable morphological features, such as cryptic colouration, extreme body flattening and lateral expansions around the body, these insects became known as Neotropical bark bugs. These characteristics also make them easily recognisable; nonetheless, the correct identification of the species is still tricky, even more so for the nymphs. In this work, we clarify the identity of the species, present new diagnoses for the family, both genera and all species, and provide an updated identification key to both adults and nymphs of the three species. We also describe and illustrate chromatic variation in Phloea subquadrata Spinola, 1837, and high-resolution photos of the three species and important diagnostic characters are provided. Literature information is synthesised and updated, and an exhaustive synonymic list is provided for the three species, including two nomenclatural corrections: Phloeocoris paradoxus Burmeister, 1835 is removed from synonymy with Phloeophana longirostris (Spinola, 1837) and considered a new junior synonym of Phloea corticata (Drury, 1773); and Phlaea paradoxa Signoret, 1863 is removed from synonymy with Phloea corticata and considered a new junior synonym of Phloeophana longirostris. Lastly, we review the distribution of the species based on collection specimens and citizen science data and, for the first time, present distribution maps for the three species of Phloeidae.
Effect of MgO recombination barrier layer on the performance of monolithic-structured solid-state dye sensitized solar cells

ABSTRACT In this paper, the optical, structural and electrical properties of pure and magnesium-doped TiO2 nanoparticles (NPs) of different cycles (2, 4, 6 and 8 cycles) were explored systematically. The magnesium-doped TiO2 was synthesised through successive ionic layer adsorption and reaction (SILAR) and deployed into dye sensitised solar cells. The effects of the MgO barrier layer was evaluated . The results show enhanced optical properties with MgO coating with a diminished band gap energy. The X-ray diffraction studies show that the anatase phase was preserved after doping and the dopant does not change the crystalline phase of the TiO2. The SEM results show well-dispersed morphology. For the device with 4 SILAR cycles of MgO, gains in open-circuit voltage, current density and simultaneous increase in eﬃciency were observed which is attributed to improved charge collection eﬃciency as electrons diﬀusing through TiO2 have a better chance of reaching the electrode before recombining. At greater SILAR cycles (6 and 8), losses in photocurrent caused net decrease in eﬃciencies. The results presented in this report implies that the modification of TiO2 with a metal oxide (MgO) can result to good photon management.
A Landscape Approach to Determining and Predicting Juvenile Coho Salmon ( Oncorhynchus kisutch ) Movement Timing and Growth Patterns Prior to Ocean Entry

i Acknowledgements . iii List of Tables . vii List of Figures . ix : Introduction . 1 : Landscape and fish size predictors of juvenile coho salmon (Oncorhynchus kisutch) movement timing and growth . 7 Introduction . 7 Methods. 12 Study Area . 12 Coho Salmon . 13 Food Availability and In-Stream Habitat . 18 Landscape Influences . 21 Statistical Analysis . 23 Results . 26 Discussion . 31 Movement . 32 Growth . 37 Implications . 38 Tables . 41 Figures. 46 : Documenting diversity: Evidence of multiple life history strategies across the North American range of coho salmon (Oncorhynchus kisutch). 60 Introduction . 60 Methods. 63 Results . 68 Discussion . 71 Commonalities and Gaps in Knowledge . 71 Patterns in Movement Strategies . 73 Patterns in Growth . 74 Implications . 76 Tables . 79 Figures. 84 : Conclusions . 89 References . 94 Appendix A: PIT antenna site design and detection metrics . 106 Appendix B: Landscape and in-stream habitat methods and data summaries . 107 vi Appendix C: PCA supporting data for Chapter 2 and Chapter 3 results . 115 Appendix D: Random forest model supporting data . 121 Appendix E: Directional classification supporting data . 122
Continuous participation in voluntary groups as a protective factor for the psychological well-being of adults who develop functional limitations: evidence from the national survey of families and households.

OBJECTIVES Although previous studies have indicated that declining functional health is associated with individuals' poorer psychological well-being, few studies have examined factors that can protect adults from the loss of well-being following functional decline. Guided by continuity theory, this study investigated the extent to which continuous participation in voluntary groups (recreational, religious, and civic) buffers individuals against the harmful psychological effects of developing functional limitations. METHODS Longitudinal data came from 4,646 respondents aged 35 to 92 in the National Survey of Families and Households (1987-1993) who reported having no functional limitations at Time 1. RESULTS Multivariate models controlling for sociodemographic factors, as well as psychological well-being at Time 1, indicated that developing functional limitations over a 5-year period was associated with greater increases in depressive symptoms and lower levels of personal growth. Increases in depressive symptoms, however, were less severe among men who were continuously involved in recreational groups than among men who were not continuously involved in recreational groups. Additionally, the association between developing functional limitations and lower levels of personal growth did not hold for men or women who continuously participated in religious groups. DISCUSSION Findings suggest that continuous participation in certain types of voluntary groups can moderate the problematic effects of developing functional limitations on psychological well-being.
Current diversity, historical analysis, and biotic integrity of fishes in the lower Potomac basin in the vicinity of Plummers Island, Maryland: Contribution to the natural history of Plummers Island, Maryland XXVII

The Plummers Island, Maryland, area has one of the more intensively studied biotas in the world. Abundant historical data on fishes of the Potomac River and tributaries, dating from the late 1800s and vouchered by museum specimens, in combination with sampling conducted in this investigation and by other recent investigators, has facilitated a definitive historical analysis of fish diversity in the region. Extensive changes in the integrity of that fauna through both extirpation of native species and addition of non-natives are documented. Eighty-six species have been recorded from the study area. It had a moderately diverse native fish fauna of 56-61 species of which 40 maintain viable populations today. Up to 30 non-native species were naturalized in the area for a time, or repeatedly introduced, and 22 remain. Enigmatic distribution patterns in the Fall Line ecotonal area may owe to a combination of gradient profiles in tributaries and Pleistocene history. There are indications that the C & O Canal may have played a role in dispersal of lowland species through and beyond the study area. These complex distributions have implications regarding the applicability of regional indices of biotic integrity criteria to studies of these streams. Sampling protocols and indices of biotic integrity, strongly based in historic data and tailored to individual streams, were devised to provide an easily repeatable method for present and future monitoring of fish assemblages and assessing stream health in Potomac tributaries in the study area. Those indices currently indicate depressed biotic integrity in these streams and generally corroborate declines documented in the historical analysis. It is recommended that these sampling procedures be repeated at future dates to monitor trends and to provide guidance for environmental planners.
Burden of drug-resistant tuberculosis among contacts of index cases: a protocol for a systematic review

Introduction People having close contact with drug-resistant tuberculosis (DR-TB) patients are at increased risk of contracting and developing the disease. However, no comprehensive review has been undertaken to estimate the burden of DR-TB among contacts of DR-TB patients. Therefore, the current systematic review will quantify the prevalence and incidence of DR-TB among contacts of DR-TB patients. Method and analysis Systematic searches will be conducted in Medline, Embase, Web of Science, Scopus, Cochrane Central Register of Controlled trials (CENTRAL) and Cumulative Index to Nursing and Allied Health Literature (CINHAL) databases. The search will be conducted without restrictions on time, language and geography. A random-effects meta-analysis will be conducted for effect estimates. The pooled prevalence and incidence of DR-TB will be compared between people with and without contact with DR-TB patients. The presence of heterogeneity between studies will be assessed by Higgins I2 statistics. Subgroup analysis will be conducted to determine the source of heterogeneity. The risk of bias will be assessed using a visual inspection of the funnel plot and Egger’s regression test statistics. Trim and fill analysis will be done in the presence of publication bias. A sensitivity analysis will be conducted by trimming low-quality studies. The systematic review will be reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol guidelines. Ethics and dissemination Ethical approval will not be required for this study as it will be a systematic review and meta-analysis based on previously published evidence. The findings of the systematic review will be presented at scientific conferences and published in scientific journals. Protocol registration The protocol is published in PROSPERO with registration number CRD42023390339.
How do they cope? A national cross-sectional study of coping in hospital doctors in Ireland

Objectives To measure coping strategies and associated psychological distress, burnout and work ability in hospital doctors in Ireland. Design National cross-sectional study of randomised sample of trainee and consultant hospital doctors. Setting Irish publicly funded hospitals and residential institutions. Participants 1749 doctors returned surveys (55% response rate). Outcome measures Dependent variables were psychological distress (measured using 12-item General Health Questionnaire), burnout (Maslach Burnout Inventory) and work ability (single-item measure). Adaptive and maladaptive coping strategies (Brief Coping Orientation to Problems Experienced) were covariates. Results The coping mechanism most frequently reported by this cohort was the adaptive strategy of active planning. Increased mean hours worked (MHW) (OR 1.02; 95% CI 1.01 to 1.03), a low Work Ability Score (OR 3.23; 95% CI 2.47 to 4.23) and maladaptive coping strategies (OR 1.26; 95% CI 1.22 to 1.31) were significantly associated with psychological distress. Adaptive coping was associated with decreased psychological distress (OR 0.98; 95% CI 0.97 to 1.00). Increased MHW (OR 0.98; 95% CI 0.97 to 0.99), insufficient work ability (OR 0.62; 95% CI 0.48 to 0.80) and maladaptive coping (OR 0.87; 95% CI 0.85 to 0.89) were significantly associated with burnout. Increased MHW (OR 0.99; 95% CI 0.98 to 1.00) and maladaptive coping (OR 0.90, 95% CI 0.88 to 0.92) were significantly associated with insufficient work ability. Conclusions Adaptive coping is associated with decreased psychological distress but does not mitigate the effect of increased work hours, which are associated with burnout, distress and insufficient work ability, regardless of a doctor’s coping style. The burden of psychological distress on doctors cannot be mitigated meaningfully unless workplace factors are addressed.
YouChoose: A Lightweight Anonymous Proof of Account Ownership

We explore the issue of anonymously proving account ownership (anonymous PAO). Such proofs allow a prover to prove to a verifier that it owns a valid account at a server without being tracked by the server or the verifier, without requiring any changes at the server’s end and without even revealing to it that any anonymous PAO is taking place. This concept is useful in sensitive applications like whistleblowing. The first introduction of anonymous PAOs was by Wang et al., who also introduced the secure channel injection (SCI) protocol to realize anonymous PAO in the context of email account ownership. In this paper, we propose YouChoose, an approach that improves upon Wang et al.’s SCI-based anonymous PAO. Unlike SCI, which demands carefully designed multi-party computation (MPC) protocols for efficiency, YouChoose works without MPC, simply relying on the verifier to selectively forward TLS records. It is faster, more efficient, and more adaptable compared to SCI. Further, the simplicity of the YouChoose approach readily enables anonymous PAO in different settings such as various ciphersuites of TLS, account types other than email, etc., while the SCI approach needs specifically designed MPC protocols for each use case. We also provide formal security definitions for a generalized anonymous PAO of which both YouChoose and SCI are concrete instantiations.
UvA-DARE (

There is an increased awareness that the performance of boards (good governance) is not only determined by structural determinants but by behavioral determinants as well. These behavioral determinants might be particularly important for public and nonprofit governance, where the role of the board is more diffuse and heterogeneous than in corporate governance. Here we investigate how social dynamics within boards in secondary education influence their performance. We follow a concise model that includes cognitive conflict, the use of expertise, effort norms, and social cohesion as determinants of board task performance. A survey among all secondary schools in the Netherlands serves as the empirical underpinning for this process-oriented model of good governance. We show that the behavioral determinants have different effects on the control task and advice task of boards. Also, we find that cognitive conflicts in supervisory boards do not lead to less but rather to more social cohesion within boards. Building on these findings, we suggest a revised model of the behavioral determinants of nonprofit board performance
Universal Analytical Forms for Modeling Image Probabilities

Seeking universal probability models for image representations, we employ a spectral approach where the images are decomposed using several bandpass lters, and probability models on the lter outputs (or spectral components) are imposed. We apply a (two-parameter) analytical form, introduced in [9] and called a Bessel K form, for modeling the marginal probabilities of these spectral components, and demonstrate their t to the observed histograms for video, IR, and range images. A relationship between the Bessel parameters and certain characteristics of the imaged objects is established. Using an expression for L-metric on the set of Bessel K forms, we suggest a pseudo-metric on the image space for quantifying image similarities/di erences. Some applications, including clutter classi cation and pruning of hypotheses for target recognition, are presented.
Degradation of Crude Oil and PAHs in Iron–Manganese Concretions and Sediment from the Northern Baltic Sea

ABSTRACT The ability of different sea bottom types to recover from oil contamination under oxic and anoxic conditions is poorly known in the brackish Baltic Sea. We carried out microcosm experiments to examine the capacity of iron–manganese concretions and sediment to remove petroleum compounds at 10°C. The biological degradation potential of polycyclic aromatic hydrocarbons (PAHs) was indicated by the 1000-fold increase in the copy numbers of PAH-degradation genes resulting in 2.2 × 106 gene copies g−1 DW. In the experiments 35−81% of the crude oil and 96% of PAHs disappeared through abiotic and biotic pathways, and there was little difference between the concretions and sediment. Bacterial community analysis revealed that the bacterial sequences obtained from the oil-treated concretions were affiliated to groups typical for concretions and metal-rich environments, whereas oil-treated sediment sequences were similar to those originating from sediments and oil-contaminated environments. The high frequency of concretion clones affiliated with specific taxonomic groups of α-, β-, γ-, and δ-proteobacteria may indicate the existence of new clades of bacteria within the Rhizobiales and Rhodospirillales of the α-proteobacteria, Burkholderiales—incertae sedis of the β-proteobacteria, Chromatiales of the γ-proteobacteria and the Syntrophobacteriales of the δ-proteobacteria. Our study suggests that concretions and bottom sediment maintain rich, distinct bacterial communities under oil exposure that have the potential to remove petroleum compounds in oxic and anoxic conditions.
Latent Classes of Lifetime Sexual Victimization Characteristics in Women in Emerging Adulthood: Differential Relations With Emotion Dysregulation

Objectives: The aims of the present study were to investigate latent classes of sexual victimization among young adult women based on characteristics of their victimization experiences (e.g., relationship with the perpetrator, nature of act, and frequency) and examine differences in dimensions of emotion dysregulation across these classes and among nonvictims. Method: Participants were 491 women in the age range of 18–25 years from the United States; of these, 335 participants (M = 22.0, SD = 2.22) reported at least one experience of sexual victimization during their lifetime. Latent class analysis was used to identify groups of women based on characteristics of their sexual victimization experiences. Results: A 3-class solution was found to be most parsimonious. The classes were labeled as high-severity developmental revictimization (DRV; 43.3%), low-severity child/adolescent sexual abuse (CASA; 20.3%), and low-severity adult sexual assault (ASA; 36.4%). The DRV class reported higher rates of penetrative abuse and longer duration of abuse than the CASA class, and higher rates of injury during assault than the ASA class. Further, the DRV class reported greater difficulties in 3 dimensions of emotion regulation than the ASA class and greater deficits in emotional clarity than the CASA class. Finally, the 3 latent classes reported greater difficulties in at least 4 dimensions of emotion regulation than the nonvictimized group. Conclusions: Findings of different classes of sexual victimization suggest the multidimensionality of these experiences. Results also highlight the potential utility of interventions aimed at improving emotion regulation among women with severe childhood sexual abuse.