Miracle-dz/UniFAR-FTUs huggingface dataset:
Strategies and Advancement in Antibody-Drug Conjugate Optimization for Targeted Cancer Therapeutics

Antibody-drug conjugates utilize the antibody as a delivery vehicle for highly potent cytotoxic molecules with specificity for tumor-associated antigens for cancer therapy. Critical parameters that govern successful antibody-drug conjugate development for clinical use include the selection of the tumor target antigen, the antibody against the target, the cytotoxic molecule, the linker bridging the cytotoxic molecule and the antibody, and the conjugation chemistry used for the attachment of the cytotoxic molecule to the antibody. Advancements in these core antibody-drug conjugate technology are reflected by recent approval of Adectris® (anti-CD30-drug conjugate) and Kadcyla® (anti-HER2 drug conjugate). The potential approval of an anti-CD22 conjugate and promising new clinical data for anti-CD19 and anti-CD33 conjugates are additional advancements. Enrichment of antibody-drug conjugates with newly developed potent cytotoxic molecules and linkers are also in the pipeline for various tumor targets. However, the complexity of antibody-drug conjugate components, conjugation methods, and off-target toxicities still pose challenges for the strategic design of antibody-drug conjugates to achieve their fullest therapeutic potential. This review will discuss the emergence of clinical antibody-drug conjugates, current trends in optimization strategies, and recent study results for antibody-drug conjugates that have incorporated the latest optimization strategies. Future challenges and perspectives toward making antibody-drug conjugates more amendable for broader disease indications are also discussed.
Biomechanical consequences of scaling

SUMMARY To function over a lifetime of use, materials and structures must be designed to have sufficient factors of safety to avoid failure. Vertebrates are generally built from materials having similar properties. Safety factors are most commonly calculated based on the ratio of a structure's failure stress to its peak operating stress. However, yield stress is a more likely limit, and work of fracture relative to energy absorption is likely the most relevant measure of a structure's safety factor, particularly under impact loading conditions characteristic of locomotion. Yet, it is also the most difficult to obtain. For repeated loading, fatigue damage and eventual failure may be critical to the design of biological structures and will result in lower safety factors. Although area:volume scaling predicts that stresses will increase with size, interspecific comparisons of mammals and birds show that skeletal allometry is modest, with most groups scaling (l∝d0.89) closer to geometric similarity (isometry: l ∝d1.0) than to elastic similarity (l ∝d0.67) or stress similarity (l ∝d0.5). To maintain similar peak bone and muscle stresses, terrestrial mammals change posture when running, with larger mammals becoming more erect. More erect limbs increases their limb muscle mechanical advantage (EMA) or ratio of ground impulse to muscle impulse (r/R=∫G/∫Fm). The increase in limb EMA with body weight (∝W0.25) allows larger mammals to match changes in bone and muscle area (∝W0.72-0.80) to changes in muscle force generating requirements (∝W0.75), keeping bone and muscle stresses fairly constant across a size range 0.04-300 kg. Above this size, extremely large mammals exhibit more pronounced skeletal allometry and reduced locomotor ability. Patterns of ontogenetic scaling during skeletal growth need not follow broader interspecific scaling patterns. Instead, negative allometric growth (becoming more slender) is often observed and may relate to maturation of the skeleton's properties or the need for younger animals to move at faster speeds compared with adults. In contrast to bone and muscle stress patterns, selection for uniform safety factors in tendons does not appear to occur. In addition to providing elastic energy savings, tendons transmit force for control of motion of more distal limb segments. Their role in elastic savings requires that some tendons operate at high stresses (and strains), which compromises their safety factor. Other `low stress' tendons have larger safety factors, indicating that their primary design is for stiffness to reduce the amount of stretch that their muscles must overcome when contracting to control movement.
Iterative Decoding of Concatenated Codes: A Tutorial

The turbo decoding algorithm of a decade ago constituted a milestone in error-correction coding for digital communications, and has inspired extensions to generalized receiver topologies, including turbo equalization, turbo synchronization, and turbo CDMA, among others. Despite an accrued understanding of iterative decoding over the years, the "turbo principle" remains elusive to master analytically, thereby inciting interest from researchers outside the communications domain. In this spirit, we develop a tutorial presentation of iterative decoding for parallel and serial concatenated codes, in terms hopefully accessible to a broader audience. We motivate iterative decoding as a computationally tractable attempt to approach maximum-likelihood decoding, and characterize fixed points in terms of a "consensus" property between constituent decoders. We review how the decoding algorithm for both parallel and serial concatenated codes coincides with an alternating projection algorithm, which allows one to identify conditions under which the algorithm indeed converges to a maximum-likelihood solution, in terms of particular likelihood functions factoring into the product of their marginals. The presentation emphasizes a common framework applicable to both parallel and serial concatenated codes.
A constitutive law for trabecular bone

Motivated by applications in orthopaedic surgery, new constitutive laws for trabecular (or spongious) bone are developed in the framework of continuum mechanics, implemented in a mechanical analysis computer program, validated by a number of in vitro experiments and illustrated by the simulation of a femoral total hip component. Current knowledge about the morphological and mechanical properties of trabecular bone is reviewed for setting the background and clarifying the contributions of the thesis. Comprehensive 1D and 3D theoretical models based on the approach of standard generalized materials are developed with a specific attention towards irreversible phenomena. The 1D model includes linear elasticity and rate-independent as well as rate-dependent plastic strain flow with damage. Based on a second order fabric tensor, the 3D model includes inhomogeneous, orthotropic linear elasticity and rate-independent plasticity with damage. In order to solve boundary value problems involving complex bone or bone-implant structures, implicit projection algorithms are developed for integrating the plastic flow rules with damage and implemented in the computer program TACT combining the finite element method, the linear iteration method and the finite difference method. The resulting numerical models are illustrated by the means of traction, bending and torsion benchmark tests. A number of pilot in vitro experiments are undertaken on human and bovine trabecular bone specimens in order to validate the theoretical models and identify the material constants. Quasistatic uniaxial and torsion experiments are performed with a method avoiding artefacts due to the inhomogeneous boundary conditions associated with porosity. Anisotropic elasticity, plasticity and damage of trabecular bone prove to be successfully described by the models in terms of structural density and morphology. Finally, the 3D constitutive law is applied to the biomechanical problem of primary stability of a cementless femoral total hip component in order to illustrate its potential.
Water data to answer urgent water policy questions: Monitoring design, available data, and filling data gaps for determining whether shale gas development activities contaminate surface water or groundwater in the Susquehanna River Basin

1 Executive Summary Throughout its history, the United States has made major investments in assessing natural resources, such as soils, timber, oil and gas, and water. These investments allow policy makers, the private sector and the American public to make informed decisions about cultivating, harvesting or conserving these resources to maximize their value for public welfare, environmental conservation and the economy. As policy issues evolve, new priorities and challenges arise for natural resource assessment, and new approaches to monitoring are needed. For example, new technologies for oil and gas development or alternative energy sources may present new risks for water resources both above and below ground. There is a need to evaluate whether today’s water monitoring programs are generating the information needed to answer questions surrounding these new policy priorities.
Gaining computational literacy by creating hybrid aesthetic learning spaces

Although the technical skills of pupils are quite high, the current approach to gain media literacy still focuses on updating software applying skills, rather than exploring the potential for learning and the nature of digital media as programmed entities. Most educational research was focussed on the computer simply as a tool or a resource, rather than on the idea of making transparent informatic modeling. It discusses the impact of self-made hybrid learning environments to establish a multidimensional media literacy involving different human senses, aesthetic objects and artefacts.
Confronting the Synchronization Problem of Semantic Region Under Geometric Attacks

In this paper, an affine invariant watermarking scheme, robust to geometric attacks, is proposed and applied to face regions. Initially, face regions are unsupervisedly extracted from an initial image and a normalization procedure, invariant to geometric attacks is applied on each of these regions using a set of specific moment criteria. A spread spectrum-based DS-CDMA watermarking scheme is then used in order to provide a multi bits watermark. The multi bits watermark embedding and detection procedures are then applicable to each normalized face region. Finally, performance of the proposed face regions watermarking scheme is tested under various distortions, providing efficient and robust watermark retrieval
Single-incision laparoscopic cholecystectomy versus multi-incision laparoscopic cholecystectomy: a meta-analysis of randomized clinical trials.

BACKGROUND Single-incision laparoscopic cholecystectomy (SILC) is theoretically supposed to be associated with better cosmetic results and less surgical-site pain than multi-incision laparoscopic cholesystectomy (MILC). So far, several relevant randomized controlled trials (RCTs) have been reported, but the results are conflicting. MATERIALS AND METHODS Meta-analysis was conducted with all the qualified RCTs comparing SILC with MILC. The databases include PubMed, EmBase, and the Cochrane Library, and the censor data were collected up to November 2011. The analyzed outcome variables included postoperative pain score, analgesia requirements, morbidity, conversion rate, operative time, postoperative hospital stay, and postoperative cosmetic score. Analyses were based on the intention-to-treat principle, if possible. All the calculations and statistical tests were performed using ReviewerManager version 5.1. 2 software. RESULTS Nine trials with a total of 755 patients (SILC in 400 patients, MILC in 355 patients) were identified and analyzed. SILC resulted in significantly longer operative time (P=.005) and higher postoperative cosmetic score on Day 30 after operation (P<.00001). There was no statistically significant difference between the groups in terms of postoperative pain score, analgesia requirements, morbidity, conversion rate, and postoperative hospital stay. CONCLUSIONS Based on the current meta-analysis, SILC appears to be as safe and effective as MILC to remove the gallbladder and results in a longer operative time and higher cosmetic satisfaction on Day 30 after surgery.
In Vivo 31P NMR measurement of glucose‐6‐phosphate in the rat muscle after exercise

Comparison of 31P NMR spectra of the rat gastrocnemius, obtained in vivo and from PCA extracts, after electrically induced contractions, demonstrates that glucose‐6‐phosphate (G6P) is the major metabolite in the low‐field part of the PME spectral region. In vivo 31P NMR can thus be used to measure the muscle G6P concentration after exercise.
Measuring the Effect of Emotions on Esophageal Motility

&NA; A preliminary study of the relationship between emotional state and esophageal motor function was undertaken. The study involved recording esophageal motility during unstructured psychiatric interviews. A significant relationship between affectively charged material and nonpropulsive activity in the esophagus was consistently found in 2 of 5 subjects and, during some interviews, in other subjects. The method is feasible and reproducible.
A simple procedure for preparation of antiserum to hepatitis-associated antigen by use of immune tolerance to serum proteins.

Monospecific antisera to hepatitis-associated, or Australia, antigen (HAA) were obtained from 16 of 22 guinea pigs that were made tolerant to globulins from human serum and immunized with partially purified HAA incorporated in complete Freund's adjuvant. The antisera were used successfully for identification of HAA in sera and hepatic tissue by immunodiffusion, complement fixation, and fluorescent antibody tests.
Health insurance and mortality in US adults.

OBJECTIVES A 1993 study found a 25% higher risk of death among uninsured compared with privately insured adults. We analyzed the relationship between uninsurance and death with more recent data. METHODS We conducted a survival analysis with data from the Third National Health and Nutrition Examination Survey. We analyzed participants aged 17 to 64 years to determine whether uninsurance at the time of interview predicted death. RESULTS Among all participants, 3.1% (95% confidence interval [CI]=2.5%, 3.7%) died. The hazard ratio for mortality among the uninsured compared with the insured, with adjustment for age and gender only, was 1.80 (95% CI=1.44, 2.26). After additional adjustment for race/ethnicity, income, education, self- and physician-rated health status, body mass index, leisure exercise, smoking, and regular alcohol use, the uninsured were more likely to die (hazard ratio=1.40; 95% CI=1.06, 1.84) than those with insurance. CONCLUSIONS Uninsurance is associated with mortality. The strength of that association appears similar to that from a study that evaluated data from the mid-1980s, despite changes in medical therapeutics and the demography of the uninsured since that time.
Language Resources Factory: case study on the acquisition of Translation Memories

This paper demonstrates a novel distributed architecture to facilitate the acquisition of Language Resources. We build a factory that automates the stages involved in the acquisition, production, updating and maintenance of these resources. The factory is designed as a platform where functionalities are deployed as web services, which can be combined in complex acquisition chains using workflows. We show a case study, which acquires a Translation Memory for a given pair of languages and a domain using web services for crawling, sentence alignment and conversion to TMX.
Use of Polymerase chain Reaction for Cryptococcus neoformans GenomeDetection in Cerebrospinal Fluid for Neurocryptococcosis Diagnosis

Cryptococcosis is a systemic infection caused by encapsulated yeast of Cryptococcus genus, has a worldwide distribution, affecting about 1/3 of human immunodeficiency virus (HIV) carriers and thus, is considered an opportunistic infection. Rapid and specific diagnostic tests for fungal infections are extremely important to effective treatment of infected patients. With the progress of molecular biology has been possible to develop new techniques for diagnosis and Cryptococcus spp identification. This study aimed standardizes a Cryptococcus spp DNA extraction method; determine the detection limit of fungus genome by PCR (Polymerase Chain Reaction) technique and determine the sensitivity and specificity of this technique in biological samples from infected patients. To standardize the DNA extraction were compared two ways for breaking fungus cell wall: the first one, using only glass beads, and the second one, using CTAB reagent. For standardization of conventional PCR and real time PCR (q-PCR), primers previously described were used, specific for Cryptococcus genus (CN4-CN5). A culture of C. neoformans (ATCC 24067) was used as a positive control. For q-PCR standardization for Cryptococcus spp genome detection and quantification in cerebrospinal fluid (CSF) were used 56 samples collected from positive neurocryptococcosis patients, which diagnostic was confirmed by other tests such as India ink, culture, latex and clinical findings. As negative control were used 44 CSF samples collected from negative neurocryptococcosis patients, according the same tests mentioned above. To confirm the specificity of the primers, q-PCR was tested in genomes of other fungal species. According to the results, no significant difference was observed between two DNA extraction methods, suggesting that for DNA extraction in CSF samples it is not necessary to use CTAB to lyse the fungus cell wall. The CTAB residues may inhibit the q-PCR, which is highly sensitive and requires a high degree of purity of the DNA. With respect to the detection limit, it was observed that the lowest DNA concentration detected by q-PCR was 47.0 femtograms (10-5) DNA/µL. The specificity test showed that primers were 100% specific, because it was not aligned in the other fungi species genomes tested. All 56 CSF samples of confirmed neurocryptococcosis patients were positive in q-PCR, while 18 (18.8%) CSF samples among negative neurocryptococcosis patients group were positive in q-PCR. This divergence of results can be explained by the fact that q-PCR has higher sensitivity than other tests used in cryptococcal meningitis diagnosis. Therefore, the q-PCR technique proved to be feasible for neurocryptococcosis diagnosis support, after it is well standardized, as in this study.
Abstract 2778: Fine mapping the KLK3 locus on chromosome 19q13.33 associated with prostate cancer susceptibility and PSA levels

Prostate cancer is the most commonly diagnosed non-cutaneous cancer in men in the United States with over 200,000 new cases and 30,000 deaths estimated in 2010. Measurements of serum prostate specific antigen (PSA) protein levels form the basis for a widely used test to screen men for prostate cancer. Germline variants in the gene that encodes the PSA protein (KLK3) have been shown to be associated with serum PSA levels. In genome-wide association studies (GWAS) of prostate cancer, KLK3 variants have been suggested to be prostate cancer risk factors. Based on a resequence analysis of a 56 kb region on chromosome 19q13.33, centered on the KLK3 gene, that characterized common germline variations in the region, we fine mapped this locus by genotyping tag SNPs in 3,522 prostate cancer cases and 3,338 controls from five cohort and case-control studies. The cohort studies are: the Prostate, Lung, Colon and Ovarian (PLCO) Cancer Screening Trial, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC), the American Cancer Society Prevention Study II Nutrition Cohort (CPS-II) and the Cohort of Norway (CONOR). The case-control study is the French Prostate Case-Control Study (CeRePP) which is a hospital based case-control study. This study has > 80% power to detect an association with an odds ratio of 1.25 (assuming a MAF of 0.05, a prevalence of prostate cancer = 1.5067% and alpha = 0.05). We did not observe a strong association for KLK3 variants, previously reported to confer risk for prostate cancer (rs2735839; P = 0.20). However, three highly correlated SNPs (rs17632542, rs62113212 and rs62113214) demonstrated an association with prostate cancer (P = 3.41×10 −4 , per-allele odds ratio (OR) = 0.77, 95% CI = 0.67-0.89). In particular, the signal is apparent in nonaggressive prostate cancer cases with Gleason score −5 , per-allele trend OR = 0.67, 95% CI = 0.56-0.81) but not in advanced cases with Gleason score > 8 or stage ≥ III (P = 0.31, per-allele OR = 1.12, 95% CI = 0.90-1.40). One of the three highly correlated SNPs, rs17632542, introduces a non-synonymous amino acid change in the KLK3 protein with a predicted benign or neutral functional impact. Baseline PSA levels were lower in control subjects with one or more minor alleles at any one of the three SNPs (1.12 ng/ml, 95% CI = 0.96-1.28) as compared to those with no minor alleles (1.61 ng/ml, 95% CI = 1.49-1.72) (P = 9.70×10 −5 ). Together our results suggest that germline KLK3 variants could influence the diagnosis of nonaggressive prostate cancer by influencing the likelihood of biopsy. It is possible that the KLK3 locus also contributes to prostate cancer risk, but additional studies will be needed to dissect the contribution of KLK3 to PSA and prostate risk separately. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2778. doi:10.1158/1538-7445.AM2011-2778
A novel integrated dual microneedle-microfluidic impedance flow cytometry for cells detection in suspensions

In this study, a new, simple and cost-effective impedance detection of yeast cell concentration by using a novel integrated dual microneedle-microfluidic impedance flow cytometry was introduced. The reported method for impedance flow cytometry detection utilizes embedded electrode and probe in the microfluidic device to perform measurement of electrical impedance when a presence of cells at sensing area. Nonetheless, this method requires costly and complicatedly fabrication process of electrode. Furthermore, to reuse the fabricated electrode, it also requires intensive and tedious cleaning process. Due to that, a dual microneedle integrated at the half height of the microchannel for cell detection as well as for electrical measurement was demonstrated. A commercial available Tungsten needle was utilized as a dual microneedle. The microneedle was easy to be removed from the disposable PDMS microchannel and can be reused with the simple cleaning process, such as washed by using ultrasonic cleaning. Although this device was low cost, it preserves the core functionality of the sensor, which is capable of detecting the passing cells at sensing area. Therefore, this device is suitable for low cost medical and food safety screening and testing process in developing countries.