Miracle-dz/UniFAR-FTUs huggingface dataset:
Fully Distributed and Mixed Symmetric Diagonal Dominant Solvers for Large Scale Optimization

Over the past twenty years, we have witnessed an unprecedented growth in data, inaugurating the so-called "Big Data" Epoch. Throughout these years, the exponential growth in the power of computer chips forecasted by Moore's Law has allowed us to increasingly handle such growing data progression. However, due to the physical limitations on the size of transistors we have already reached the computational limits of traditional microprocessors' architecture.Therefore, we either need conceptually new computers or distributed models of computation to allow processors to solve Big Data problems in a collaborative manner. The purpose of this thesis is to show that decentralized optimization is capable of addressing our growing computational demands by exploiting the power of coordinated data processing. In particular, we propose an exact distributed Newton method for two important challenges in large-scale optimization: Network Flow and Empirical Risk Minimization. The key observation behind our method is related to the symmetric diagonal dominant structure of the Hessian of dual functions correspondent to the aforementioned problems. Consequently, one can calculate the Newton direction by solving symmetric diagonal dominant (SDD) systems in a decentralized fashion. We first propose a fully distributed SDD solver based on a recursive approximation of SDD matrix inverses with a collection of specifically structured distributed matrices. To improve the precision of the algorithm, we then apply Richardson Preconditioners arriving at an efficient algorithm capable of approximating the solution of SDD system with any arbitrary precision. vi Our second fully distributed SDD solver significantly improves the computational performance of the rst algorithm by utilizing Chebyshev polynomials for an approximation of the SDD matrix inverse. The particular choice of Chebyshev polynomials is motivated by their extremal properties and their recursive relation. We then explore mixed strategies for solving SDD systems by slightly relaxing the decentralization This dissertation is available at ScholarlyCommons: https://repository.upenn. edu/edissertations/2617 requirements. Roughly speaking, by allowing for one computer to aggregate some particular information from all others, one can gain quite surprising computational benefits. The key idea is to construct a spectral sparsifier of the underlying graph of computers by using local communication between them. Finally, we apply these solvers for calculating the Newton direction for the dual function of Network Flow and Empirical Risk Minimization. On the theoretical side, we establish quadratic convergence rate for our algorithms surpassing all existing techniques. On the empirical side, we verify our superior performance in a set of extensive numerical simulations. Degree Type Dissertation Degree Name Doctor of Philosophy (PhD) Graduate Group Computer and Information Science First Advisor Ali Jadbabaie
Acquisition of a glycosylated B-cell receptor drives follicular lymphoma toward a dark zone phenotype

Follicular lymphoma (FL) is an indolent malignancy of mature B cells that are arrested at the germinal center (GC) stage. 1,2 In physiological GC reactions, B cells undergo clonal expansion and B-cell receptor (BCR) af ﬁ nity maturation towards antigen. B cells participating in a GC reaction commute between GC light zone (LZ) and dark zone (DZ). 3 In the LZ, B cells become activated via antigens presented on follicular dendritic cells and interactions with follicular T helper cells. DZ B cells rapidly proliferate and diversify their BCR genes by somatic hypermutation (SHM). LZ/DZ transitions are accompanied by synchronized changes in the gene expression. 4,5 These transcriptional GC programs are desynchronized in FL, but the gene expression pro ﬁ le of FL cells globally resembles LZ cells more than DZ cells. 5,6 Like healthy B cells, FL cells depend on the expression of a functional BCR. Arrest at the GC stage and constitutive expression of activation-induced cytidine deaminase
The physical spectrum of theories with a Brout-Englert-Higgs effect

The physical, observable spectrum in gauge theories is made up from gauge-invariant states. In the standard model of particle physics the Fröhlich-Morchio-Strocchi mechanism shows that these states can be adequately mapped to the gauge-dependent, elementary W , Z , and Higgs as well as fermionic states. In theories with a more general gauge group and Higgs sector this is no longer necessarily the case. We classify and predict the physical spectrum for a wide range of such theories and show that discrepancies between the spectrum of elementary elds and physical particles frequently arise. We discuss in detail SU(N) gauge theories with single scalar elds in the fundamental and adjoint representation of the gauge group. We also investigate models for grand unied theories where usually more scalar elds appear in the theory. The validity of these predictions can only be tested using non-perturbative methods. This is done using the method of lattice gauge theory for the special case where the gauge group is SU(3) with one single fundamental scalar. We rst determine the phase diagram of this theory and compute the spectrum of bound states in a regime where a Brout-Englert-Higgs eect takes place. Then the spectrum of gauge-variant, elementary elds is computed and compared to the gauge-invariant, physical spectrum. We nd that our computations seem to conrm the predictions of the Fröhlich-Morchio-Strocchi mechanism.
Nucleosome retention by histone chaperones and remodelers occludes pervasive DNA–protein binding

Abstract DNA packaging within chromatin depends on histone chaperones and remodelers that form and position nucleosomes. Cells express multiple such chromatin regulators with overlapping in-vitro activities. Defining specific in-vivo activities requires monitoring histone dynamics during regulator depletion, which has been technically challenging. We have recently generated histone-exchange sensors in Saccharomyces cerevisiae, which we now use to define the contributions of 15 regulators to histone dynamics genome-wide. While replication-independent exchange in unperturbed cells maps to promoters, regulator depletions primarily affected gene bodies. Depletion of Spt6, Spt16 or Chd1 sharply increased nucleosome replacement sequentially at the beginning, middle or end of highly expressed gene bodies. They further triggered re-localization of chaperones to affected gene body regions, which compensated for nucleosome loss during transcription complex passage, but concurred with extensive TF binding in gene bodies. We provide a unified quantitative screen highlighting regulator roles in retaining nucleosome binding during transcription and preserving genomic packaging.
Use of Payload Binding Selectivity Enhancers to Improve Therapeutic Index of Maytansinoid-Antibody-Drug Conjugates.

Systemic exposure to released cytotoxic payload contributes to the dose-limiting off-target toxicities of anti-cancer antibody-drug conjugates (ADC). In this work, we present an "inverse targeting" strategy to optimize the therapeutic selectivity of maytansinoid-conjugated ADCs. Several anti-maytansinoid sdAbs were generated via phage-display technology with binding IC50s between 10-60 nM. Co-incubation of DM4 with the anti-maytansinoid sdAbs shifted the IC50 of DM4 up to 250-fold. Tolerability and efficacy of 7E7-DM4 ADC, an anti-CD123 DM4-conjugated ADC, were assessed in healthy and in tumor-bearing mice, with and without co-administration of an anti-DM4 sdAb. Co-administration with anti-DM4 sdAb reduced 7E7-DM4 induced-weight loss, where the mean values of percentage weight loss at nadir for mice receiving ADC+saline and ADC+sdAb were 7.9±3% and 3.8±1.3% (p<0.05). In tumor-bearing mice, co-administration of the anti-maytansinoid sdAb did not negatively affect the efficacy of 7E7-DM4 on tumor growth or survival following dosing of the ADC at 1 mg/kg (p=0.49) or at 10 mg/kg (p = 0.9). Administration of 7E7-DM4 at 100 mg/kg led to dramatic weight loss, with 80% of treated mice succumbing to toxicity prior to the appearance of mortality relating to tumor growth in control mice. However, all mice receiving co-dosing of 100 mg/kg 7E7-DM4 with anti-DM4 sdAb were able to tolerate the treatment, which enabled reduction in tumor volume to undetectable levels and to dramatic improvements in survival. In summary, we have demonstrated the utility and feasibility of the application of anti-payload antibody fragments for inverse targeting to improve the selectivity and efficacy of anti-cancer ADC therapy.
Global warming and arctic terns: Estimating climate change impacts on the world's longest migration

Climate change is one of the top three global threats to seabirds, particularly species that visit polar regions. Arctic terns migrate between both polar regions annually and rely on productive marine areas to forage, on sea ice for rest and foraging, and prevailing winds during flight. Here, we report 21st‐century trends in environmental variables affecting arctic terns at key locations along their Atlantic/Indian Ocean migratory flyway during the non‐breeding seasons, identified through tracking data. End‐of‐century climate change projections were derived from Earth System Models and multi‐model means calculated in two Shared Socioeconomic Pathways: ‘middle‐of‐the‐road’ and ‘fossil‐fuelled development’ scenarios. Declines in North Atlantic primary production emerge as a major impact to arctic terns likely to affect their foraging during the 21st century under a ‘fossil‐fuelled development’ scenario. Minimal changes are, however, projected at three other key regions visited by arctic terns (Benguela Upwelling, Subantarctic Indian Ocean and the Southern Ocean). Southern Ocean sea ice extent is likely to decline, but the magnitude of change and potential impacts on tern survival are uncertain. Small changes (<1 m s−1) in winds are projected in both scenarios, but with minimal likely impacts on migration routes and duration. However, Southern Ocean westerlies are likely to strengthen and contract closer to the continent, which may require arctic terns to shift routes or flight strategies. Overall, we find minor effects of climate change on the migration of arctic terns, with the exception of poorer foraging in the North Atlantic. However, given that arctic terns travel over huge spatial scales and live for decades, they integrate minor changes in conditions along their migration routes such that the sum effect may be greater than the parts. Meeting carbon emission targets is vital to slow these end‐of‐century climatic changes and minimise extinction risk for a suite of polar species.
Instructed motivational states bias reinforcement learning and memory formation

Significance Imperative motivation helps us address urgent goals, such as escaping a threat or winning a competition. However, imperative motivation can constrain attention and memory. Conversely, interrogative motivation supports curiosity, exploration, and memory formation for future goals. Here, we tested key predictions from this theoretical framework: We varied the cover stories before a learning task to induce either imperative or interrogative motivational states, thereby influencing both reinforcement learning and subsequent memory. Our results are relevant to interventions designed to motivate immediate actions or enhance long-term memory, such as in education, behavior change, clinical practice, and science communication. Induced motivational states may shift cognitive and neural processing to support one’s goals, enhancing attention, performance, learning, or memory.
Investigating the effect of prophylactic claw trimming on the interval between calving and first observed elevated locomotion score in pasture-based dairy cows

ABSTRACT Aims To evaluate, in a pasture-based dairy herd, the response to a three-time point hoof trimming regime on lameness incidence and time from calving to observation of an elevated locomotion score (LS). Methods This study was conducted on a 940-cow spring-calving herd in New Zealand’s North Island between May 2018 and May 2019. Cows (n = 250) were randomly allocated to the hoof trimming group, with the remainder assigned to the non-trim cohort. One trained professional hoof trimmer used the five-step Dutch method to trim the hind feet of the trimming group. Throughout the subsequent production season, the whole herd was locomotion-scored fortnightly using the 4-point (0–3) Dairy NZ lameness score. Kaplan–Meier survival curves were used to assess the univariable effect of trimming on the interval between calving and first LS of ≥ 2 and first LS ≥ 1. A multivariable Cox proportional hazards regression was used to further evaluate the effect of trimming on time to elevated LS. Results Mean lameness (LS ≥ 2) prevalence was 2.6%, with 30% of cows having ≥ 4 observations during the study period when at least one LS was ≥ 2. For LS ≥ 1, mean prevalence was 40%, with 98.6% of cows having ≥ 4 observations during the study period when at least one LS was ≥ 1 during lactation. Hoof trimming had no apparent effect on the incidence of clinical lameness (LS ≥ 2) (trimmed vs. non-trimmed: 33.2% vs. 28.8%, respectively), but for LS ≥ 1, there was a small decrease in the incidence of LS ≥ 1 (trimmed vs. non-trimmed: 96.9% vs. 99.3%, respectively). The hazard of a cow having a first observed LS ≥ 2 in the control group was 0.87 (95% CI = 0.66–1.14) times that of the trimmed group; however, the hazard of a cow having a first LS ≥ 1 was 1.60 (95% CI = 1.37–1.88) times higher in the control than in the trimmed group. Conclusion and clinical relevance On this farm, prophylactic hoof trimming had no clinically relevant impact on the incidence of clinical lameness and was not associated with clinically beneficial reductions in time to first observed LS ≥ 2. This may be because claw horn imbalance was not pronounced on this farm, with 53% of cows needing no trim on either hind limb on the first trimming occasion. Further research on the response to prophylactic trimming in pasture-based dairy cattle is required.
A Cheap Trick to Improve the Power of a Conservative Hypothesis Test

ABSTRACT Critical values and p-values of statistical hypothesis tests are often derived using asymptotic approximations of sampling distributions. However, this sometimes results in tests that are conservative (i.e., understate the frequency of an incorrectly rejected null hypothesis by employing too stringent of a threshold for rejection). Although computationally rigorous options (e.g., the bootstrap) are available for such situations, we illustrate that simple transformations can be used to improve both the size and power of such tests. Using a logarithmic transformation, we show that the transformed statistic is asymptotically equivalent to its untransformed analogue under the null hypothesis and is divergent from the untransformed version under the alternative (yielding a potentially substantial increase in power). The transformation is applied to several easily-accessible statistical hypothesis tests, a few of which are taught in introductory statistics courses. With theoretical arguments and simulations, we illustrate that the log transformation is preferable to other forms of correction (such as statistics that use a multiplier). Finally, we illustrate application of the method to a well-known dataset. Supplementary materials for this article are available online.
Phthalimide as a versatile pharmacophore scaffold: Unlocking its diverse biological activities

Phthalimide, a pharmacophore exhibiting diverse biological activities, holds a prominent position in medicinal chemistry. In recent decades, numerous derivatives of phthalimide have been synthesized and extensively studied for their therapeutic potential across a wide range of health conditions. This comprehensive review highlights the latest developments in medicinal chemistry, specifically focusing on phthalimide‐based compounds that have emerged within the last decade. These compounds showcase promising biological activities, including anti‐inflammatory, anti‐Alzheimer, antiepileptic, antischizophrenia, antiplatelet, anticancer, antibacterial, antifungal, antimycobacterial, antiparasitic, anthelmintic, antiviral, and antidiabetic properties. The physicochemical profiles of the phthalimide derivatives were carefully analyzed using the online platform pkCSM, revealing the remarkable versatility of this scaffold. Therefore, this review emphasizes the potential of phthalimide as a valuable scaffold for the development of novel therapeutic agents, providing avenues for the exploration and design of new compounds.
The Burden of Attention-Deficit Hyperactivity Disorder (ADHD) in the Middle East and North Africa Region, 1990 to 2019

Objective: To report the burden of ADHD in the Middle East and North Africa (MENA) region from 1990 to 2019. Methods: Publicly available data on the burden of ADHD were retrieved from the Global Burden of Disease study 2019. The counts and age-standardized rates (per 100,000) were presented. Results: In 2019, ADHD had an age-standardized point prevalence of 1245.1 and a years lived with disability (YLD) rate of 15.1 per 100,000 in MENA, which were 7.2% (−11 to −3.3) and 7.2% (−11.2 to −2.7) lower, respectively, than in 1990. The highest YLD rate of ADHD was found in the 10 to 14 age group and there were no remarkable differences between males and females. No clear association was found between the YLD rate and the socio-demographic index. Conclusion: The burden of ADHD in the MENA region decreased over the period 1990 to 2019, and regularly updating the epidemiological information is suggested.
Need for additional training to be a laboratory genetic counselor—A qualitative exploration

Opportunities for genetic counselors to work in the laboratory have grown exponentially, yet the professional development needed to serve in these roles had not been previously explored. This study aimed to identify competencies required for entry‐level genetic counselors working in the laboratory, explore the perceived level of preparation of these competencies as noted by experts in the laboratories, and assess the perceived value of additional credentialing for genetic counselors practicing in these settings. Twenty genetic counselors working in the laboratory setting and five MD or PhD laboratory managers, identified through purposeful and snowball sampling and with at least 5 years of experience working in a laboratory, were interviewed using a semi‐structured protocol. Transcripts were analyzed thematically using deductive and inductive coding. Key findings included the distinction of laboratory and industry roles as involving nondirect patient care and differing from genetic counseling roles in the clinical setting. Genetic counselors working in the laboratory feel well prepared to transition into this setting and provide a unique patient‐focused perspective to laboratory roles, including variant interpretation, marketing, and product development. Practice‐based competencies (PBCs) were translatable to those used in the laboratory, yet variant interpretation, limitations of genomics‐based tests, and the business of health care were noted as important to these roles but not fully addressed in the PBCs. Additional skills were often developed through on‐the‐job training and interdisciplinary collaboration, but more exposure to diverse roles in genetic counseling programs' didactic and field training was recommended. The majority felt that requiring an additional post‐master's credential to work in the laboratory setting may restrict movement into these roles. Several questioned their identity as genetic counselors as they were no longer providing direct patient care and/or had been dissuaded by others from pursuing a laboratory position. Research focused on professional identity among genetic counselors working in nondirect patient care roles is warranted.
A hybrid EM scheme for the composite scattering and the SAR imaging of a low-altitude target above the electrically large and multi-scale sea surface

ABSTRACT This article has developed a feasible hybrid electromagnetic scheme to evaluate the composite scattering and the Synthetic Aperture Radar(SAR) image characteristics of a low altitude perfect electric conductor (PEC) target above the sea surface at the high microwave frequency bands. In this method, the scattering upon the target surface is calculated by the Physical Optics (PO) method; the sea surface scattering is evaluated by a Bragg Modified Small Scale Approximation (BMSSA) method; the coupling components are considered by the Geometrical Optics (GO) method with efficient ray tracing techniques; finally, the diffractions from the edged structures are considered by the Equivalent Edge Current (EEC) method. The hybrid method can give a physical insight of the composite scattering mechanisms, and it can overcome the difficulties in accurately evaluating the composite scattering characteristics of a target above the electrically large and multi-scale sea surface in the real scene. The computation model and method is validated by the exact numerical solver. Numerical results compare the scattering characteristics of a missile-like target above the electrically large sea surface in the conditions of different incident frequencies, incident angles and sea states. Finally, SAR image characteristics at different sea states are presented, with the target scattering, sea scattering and coupling scattering characteristics further discussed in details.
Vienna Cancer Stem Cell Club (VCSCC): 20 year jubilee and future perspectives

ABSTRACT Introduction The Vienna Cancer Stem Cell Club (VCSCC) was launched by a group of scientists in Vienna in 2002. Areas covered Major aims of the VCSCC are to support research on cancer stem cells (CSC) in hematopoietic malignancies and to translate CSC-related markers and targets into clinical application. A primary focus of research in the VCSCC is the leukemic stem cell (LSC). Between 2013 and 2021, members of the VCSCC established a special research program on myeloproliferative neoplasms and since 2008, members of the VCSCC run the Ludwig Boltzmann Institute for Hematology and Oncology. In all these years, the VCSCC provided a robust intellectual platform for translational hematology and LSC research in Vienna. Furthermore, the VCSCC interacts with several national and international study groups and societies in the field. Representatives of the VCSCC also organized a number of international meetings and conferences on neoplastic stem cells, including LSC, in the past 15 years, and contributed to the definition and classification of CSC/LSC and related pre-malignant and malignant conditions. Expert opinion The VCSCC will continue to advance the field and to develop LSC-detecting and LSC-eradicating concepts through which diagnosis, prognostication, and therapy of blood cancer patients should improve.