Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of a PD-L1 Complementary Diagnostic Immunohistochemistry Assay (SP142) for Atezolizumab

Cancer immunotherapies, such as atezolizumab, are proving to be a valuable therapeutic strategy across indications, including non–small cell lung cancer (NSCLC) and urothelial cancer (UC). Here, we describe a diagnostic assay that measures programmed-death ligand 1 (PD-L1) expression, via immunohistochemistry, to identify patients who will derive the most benefit from treatment with atezolizumab, a humanized monoclonal anti-PD-L1 antibody. We describe the performance of the VENTANA PD-L1 (SP142) Assay in terms of specificity, sensitivity, and the ability to stain both tumor cells (TC) and tumor-infiltrating immune cells (IC), in NSCLC and UC tissues. The reader precision, repeatability and intermediate precision, interlaboratory reproducibility, and the effectiveness of pathologist training on the assessment of PD-L1 staining on both TC and IC were evaluated. We detail the analytical validation of the VENTANA PD-L1 (SP142) Assay for PD-L1 expression in NSCLC and UC tissues and show that the assay reliably evaluated staining on both TC and IC across multiple expression levels/clinical cut-offs. The reader precision showed high overall agreement when compared with consensus scores. In addition, pathologists met the predefined training criteria (≥85.0% overall percent agreement) for the assessment of PD-L1 expression in NSCLC and UC tissues with an average overall percent agreement ≥95.0%. The assay evaluates PD-L1 staining on both cell types and is robust and precise. In addition, it can help to identify those patients who may benefit the most from treatment with atezolizumab, although treatment benefit has been demonstrated in an all-comer NSCLC and UC patient population.
International Journal of Innovative Technology and Exploring Engineering (IJITEE)

Tempeh is the most popular food in Indonesia. The process of making tempeh requires a lot of water. The preliminary analysis of tempeh wastewater showed that the value of COD, BOD and pH are 26693 mg/l, 11204 mg/l and 3,99. This results actually do not meet the Minister of Environment regulation No.5 (2014) about quality standard of wastewater treatment for industry. The quality standard for COD, BOD and PH for tempeh wastewater are 100-300 mg/l, 50-150 mg/l, and 6-9. So, the tempeh industrial wastewater must be processed before being discharged into the environment. The aim of this study is to determine the activated sludge ability to reduce COD, BOD, and also pH value in tempeh industrial wastewater. Tempeh industrial wastewater treatment carried out in aerated batch reactor using wastewater composition 10%, 15%, and 25% (v/v) of tempeh wastewater in 500 ml as a research variables. The wastewater while the hidraulic retention time is 48 hours. The highest COD, BOD removal efficiency occured at 25% (v/v) wastewater composition each for 74,58%, 79,27%. The COD and BOD concentration after treatment are 7625,79 mg/l and 4555,7 mg/l. And pH at 25% (v/v) wastewater composition is 6,92. pH value after treatment meet quality standard of industrial wastewater from Minister of Environment regulation No.5 (2014), but COD and BOD do not meet the standards.
Differences in Total Protein Concentration between Fresh and Frozen Serum and Plasma Samples Used to Assess Failure of Passive Transfer in Dairy Calves

The objectives of this study were to determine differences in total protein (TP) concentration between samples before and after freezing, and to determine the correlation between total protein in serum and plasma to evaluate passive transfer in calves. Blood was collected via jugular vein puncture from a total of 127 calves (34 Holstein and 93 Jersey) once between 1 and 3 days of age. Serum and plasma protein concentrations were measured via digital refractometer in fresh specimens; samples were then frozen for storage. After a variable period of time in storage (≤1 to 8 months), frozen samples were thawed and re-analyzed. Passing-Bablok regression showed that total protein concentration in plasma was consistently higher than in serum. Additionally, multivariate regression showed that Jersey calves had higher total protein concentration in serum than Holstein calves (0.429 ± 0.049 g/dL), and that each additional month of storage resulted in lower protein concentration in serum (-0.116 ± 0.017 g/dL). Electrophoresis showed that all protein fraction levels varied after long-term storage of serum, although albumin accounted for most of the variation. It is concluded that plasma samples can be used as a new and improved option to evaluate effectiveness of colostrum management protocols under field conditions because plasma samples are easier to handle in the field and they correlate well with fresh serum total protein concentration and are not significantly affected by frozen storage.
Neuronal migration abnormality in peroxisomal bifunctional enzyme defect

Patterns of brain dysgenesis that resemble those in the Zellweger syndrome were demonstrated in a boy with an isolated defect of the peroxisomal bifunctional enzyme. There was bilateral centrosylvian pachygyria and polymicrogyria, diffuse hemispheric hypomyelination with heterotopic neurons, Purkinje cell heterotopias, and simplified convolutions of the dentate nucleus and inferior olive. This association of Zellweger syndrome–like brain dysgenesis with a defect of a single peroxisomal enzyme provides new opportunities for the study of pathogenetic mechanisms in peroxisomal disorders.
TLR7 stimulation augments T effector‐mediated rejection of skin expressing neo‐self antigen in keratinocytes

Immunotherapy generally fails to induce tumour regression in spontaneously arising tumours. Failure is attributed to both tumour‐related factors and an ineffective immune response. As a model of tumour immunotherapy, without the confounding effects of potential tumour‐determined mechanisms of immune evasion, we studied the requirements for rejection of skin grafts expressing a neo‐self antigen in somatic cells and not in antigen‐presenting cells. When antigen expression was restricted to somatic cells, both CD4+ and CD8+ effector cells were required for graft rejection. Although freshly placed grafts were spontaneously rejected, healed grafts established under the cover of T cell depletion were not rejected even after T cell numbers recovered to a level where freshly placed grafts on the same animal were rejected, suggesting that healed skin grafts expressing a neo‐self antigen only in somatic cells could not be rejected by primed recipients with functional effector T cells. Local TLR7 ligation induced inflammatory responses and rejection of healed grafts exposed to the TLR agonist but did not induce rejection of untreated healed grafts on the same animal. Thus, local pro‐inflammatory signalling via TLR7 can promote effector T cell function against skin cells displaying their nominal antigen.
Linear subspace methods in face recognition

Despite over 30 years of research, face recognition is still one of the most difficult problems in the field of Computer Vision. The challenge comes from many factors affecting the performance of a face recognition system: noisy input, training data collection, speed-accuracy trade-off, variations in expression, illumination, pose, or ageing. Although relatively successful attempts have been made for special cases, such as frontal faces, no satisfactory methods exist that work under completely unconstrained conditions. This thesis proposes solutions to three important problems: lack of training data, speed-accuracy requirement, and unconstrained environments. The problem of lacking training data has been solved in the worst case: single sample per person. Whitened Principal Component Analysis is proposed as a simple but effective solution. Whitened PCA performs consistently well on multiple face datasets. Speed-accuracy trade-off problem is the second focus of this thesis. Two solutions are proposed to tackle this problem. The first solution is a new feature extraction method called Compact Binary Patterns which is about three times faster than Local Binary Patterns. The second solution is a multi-patch classifier which performs much better than a single classifier without compromising speed. Two metric learning methods are introduced to solve the problem of unconstrained face recognition. The first method called Indirect Neighourhood Component Analysis combines the best ideas from Neighourhood Component Analysis and One-shot learning. The second method, Cosine Similarity Metric Learning, uses Cosine Similarity instead of the more popular Euclidean distance to form the objective function in the learning process. This Cosine Similarity Metric Learning method produces the best result in the literature on the state-of-the-art face dataset: the Labelled Faces in the Wild dataset. Finally, a full face verification system based on our real experience taking part in ICPR 2010 Face Verification contest is described. Many practical points are discussed.
[Investigation of the Risk Factors Affecting Toxoplasma gondii Seropositivity in Women of Reproductive Age Applying to the Maternity Clinic of Kilis State Hospital].

OBJECTIVE The objective of the study is to detect the seroprevalence of toxoplasmosis in Kilis province, determine the risk factors for toxoplasmosis, and assess the effect of risk factors on seropositivity. METHODS The research performed in Kilis State Hospital was a cross-sectional study in which Enzyme-linked Immunosorbent Assay (ELISA) was used. The study included women between the ages of 15 and 49 years. The number of samples was 322. Female patients participating had to fill a questionnaire form of 27 questions in total, and blood samples were taken. Survey and laboratory results were uploaded to SPSS 15 program and assessed. RESULTS As results of the study, the seropositivity of anti-Toxoplasma gondii (anti-T. gondii) Immunoglobulin G (IgG) antibodies was determined to be 63.4% and that of anti-T. gondii Immunoglobulin M (IgM) antibodies was determined to be 4.0%. It was found that the seropositivity of anti-T. gondii IgG antibodies was significantly dependent on age groups, educational status, number of live births, and habits of raw or undercooked meat consumption. It was found that the IgM seroprevalence in 210 pregnant women was 3.8%, and the IgG seroprevalence was positive at 59.5%; no statistical significance could be determined in both. CONCLUSION It was determined that age distribution, income and educational levels, and eating habits of people living in the research region affect toxoplasmosis.
Targeted Next-Generation Sequencing of Cancer Genes in Advanced Stage Malignant Pleural Mesothelioma: A Retrospective Study

Introduction: Malignant pleural mesothelioma (MPM) is a rare malignant disease, and the understanding of molecular pathogenesis has lagged behind other malignancies. Methods: A series of 123 formalin-fixed, paraffin-embedded tissue samples with clinical annotations were retrospectively tested with a commercial library kit (Ion AmpliSeq Cancer Hotspot Panel v.2, Life Technologies, Grand Island, NY) to investigate 50 genes plus other two, BRCA1-associated protein-1 (BAP-1) and neurofibromatosis-2 (NF2), frequently altered in MPM. DNA was obtained from tissues after manual microdissection and enriched for at least 50% cancer cells. Variations affecting protein stability or previously correlated to cancer, more frequently identified (≥25 patients with at least 10% of allelic frequency), were subsequently evaluated by Sanger sequencing. Immunohistochemistry staining for BAP1 and NF2 proteins was also performed. Results: The commonest genetic variations were clustered in two main pathways: the p53/DNA repair (TP53, SMACB1, and BAP1) and phosphatidylinositol 3-kinase–AKT pathways (PDGFRA, KIT, KDR, HRAS, PIK3CA, STK11, and NF2). PIK3CA:c.1173A>G mutation, STK11:rs2075606 (T>C), or TP53:rs1042522 (Pro/Pro) was significantly associated with time to progressive disease (TTPD; all p values < 0.01). Furthermore, the accumulation of genetic alterations correlated with shorter TTPD and reduced overall survival (TTPD p value = 0.02, overall survival p value = 0.04). BAP1 genetic variations identified were mainly located in exons 13 and 17, and BAP1 nonsynonymous variations were significantly correlated with BAP1 protein nuclear localization. Conclusion: Next-generation sequencing was applied to a relatively large retrospective series of MPM using formalin-fixed, paraffin-embedded archival material. Our results indicate a complex mutational landscape with a higher number of genetic variations in the p53/DNA repair and phosphatidylinositol 3-kinase pathways, some of them with prognostic value.
Analysis of the sorting signals directing NADH-cytochrome b5 reductase to two locations within yeast mitochondria

Mitochondrial NADH-cytochrome b5 reductase (Mcr1p) is encoded by a single nuclear gene and imported into two different submitochondrial compartments: the outer membrane and the intermembrane space. We now show that the amino-terminal 47 amino acids suffice to target the Mcr1 protein to both destinations. The first 12 residues of this sequence function as a weak matrix-targeting signal; the remaining residues are mostly hydrophobic and serve as an intramitochondrial sorting signal for the outer membrane and the intermembrane space. A double point mutation within the hydrophobic region of the targeting sequence virtually abolishes the ability of the precursor to be inserted into the outer membrane but increases the efficiency of transport into the intermembrane space. Import of Mcr1p into the intermembrane space requires an electrochemical potential across the inner membrane, as well as ATP in the matrix, and is strongly impaired in mitochondria lacking Tom7p or Tim11p, two components of the translocation machineries in the outer and inner mitochondrial membranes, respectively. These results indicate that intramitochondrial sorting of the Mcr1 protein is mediated by specific interactions between the bipartite targeting sequence and components of both mitochondrial translocation systems.
Tense marking in children with autism

A recent large-scale study identified a subgroup of children with autism who had a language profile similar to that found among children with specific language impairment (SLI), including difficulties with nonsense word repetition, an ability that has been implicated as one clinical marker for SLI. A second clinical marker for English-speaking children with SLI is high rates of omission of grammatical morphemes that mark tense in obligatory contexts. This study used experimental probes designed to elicit third person and past tense morphology with a large heterogeneous sample of children with autism. The subgroup of children with autism who were language impaired showed high rates of omission of tense marking on the experimental tasks. In addition, some of the children with autism made performance errors that were specific to the autistic population, such as echolalia. These findings further refine the characteristics of language impairment found in a subgroup of children with autism.
Mea Culpa: Predicting Stock Prices From Organizational Attributions

People’s causal attributions for events in their lives have been shown to relate to individual and interpersonal outcomes. Groups and organizations also make causal attributions, and this article examines whether their publicly communicated attributions predict organizational-level outcomes. By content analyzing attributions contained in corporate annual reports from 14 companies during a 21-year period, the authors found that organizations that made “self disserving” attributions— internal and controllable attributions for negative events—had higher stock prices 1 year later. The authors argue that claiming personal responsibility for negative events made the organizations appear more in control, leading to more positive impressions.
H∞ analysis of positive continuous systems with time-delay

This paper addresses the problem of the H∞ analysis of positive continuous systems with time-delay. The corresponding bounded real lemma is newly characterized in terms of linear matrix inequalities, in which Lyapunov matrix can be diagonal. Based on the separation theorem of convex set in Euclidean space, we prove that the delay size has no influence on the bounded real lemma of such systems.
A new on-wafer de-embedding technique for on-chip rf transmission line interconnect characterization

Absfracf This paper introduces a new de-embedding method for on-chip RF transmission line characterization. The new technique allows subtraction of pad parasitics based on measurements of only two LI=L and Lz=N.L (N being a discrete number) long transmission lines with attached measurement pads. No dummy “open”, “short” and “thru” devices are required. The new method has also been extended for the case when Lz#N.L, and only L,, L2 and AL= L,-L, long interconnects with attached pads are available on the test wafer. The proposed methodology has been compared with several well-known de-embedding approaches (“thru”, “open-short” aed “short-open“) and with simulation results from the industry standard electromagnetic solver (lE3D) for de-embedding of on-chip interconnects at frequencies up to 70GHz. Index Terms -Transmission Line interconnect, on-wafer measurement, S-parameters, de-embedding.
Extended healing validation of an artificial tendon to connect the quadriceps muscle to the Tibia: 180‐day study

Whenever a tendon or its bone insertion is disrupted or removed, existing surgical techniques provide a temporary connection or scaffolding to promote healing, but the interface of living to non‐living materials soon breaks down under the stress of these applications, if it must bear the load more than acutely. Patients are thus disabled whose prostheses, defect size, or mere anatomy limit the availability or outcomes of such treatments. Our group developed the OrthoCoupler™ device to join skeletal muscle to prosthetic or natural structures without this interface breakdown. In this study, the goat knee extensor mechanism (quadriceps tendon, patella, and patellar tendon) was removed from the right hind limb in 16 goats. The device connected the quadriceps muscle to a stainless steel bone plate on the tibia. Mechanical testing and histology specimens were collected from each operated leg and contralateral unoperated control legs at 180 days. Maximum forces in the operated leg (vs. unoperated) were 1,400 ± 93 N (vs. 1,179 ± 61 N), linear stiffnesses were 33 ± 3 N/mm (vs. 37 ± 4 N/mm), and elongations at failure were 92.1 ± 5.3 mm (vs. 68.4 ± 3.8 mm; mean ± SEM). Higher maximum forces (p = 0.02) and elongations at failure (p = 0.008) of legs with the device versus unoperated controls were significant; linear stiffnesses were not (p = 0.3). We believe this technology will yield improved procedures for clinical challenges in orthopedic oncology, revision arthroplasty, tendon transfer, and tendon injury reconstruction. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1112–1117, 2012
Induction of the ferritin gene (ftnA) of Escherichia coli by Fe2+–Fur is mediated by reversal of H‐NS silencing and is RyhB independent

FtnA is the major iron‐storage protein of Escherichia coli accounting for ≤50% of total cellular iron. The FtnA gene (ftnA) is induced by iron in an Fe2+–Fur‐dependent fashion. This effect is reportedly mediated by RyhB, the Fe2+–Fur‐repressed, small, regulatory RNA. However, results presented here show that ftnA iron induction is independent of RyhB and instead involves direct interaction of Fe2+–Fur with an ‘extended’ Fur binding site (containing five tandem Fur boxes) located upstream (−83) of the ftnA promoter. In addition, H‐NS acts as a direct repressor of ftnA transcription by binding at multiple sites (I–VI) within, and upstream of, the ftnA promoter. Fur directly competes with H‐NS binding at upstream sites (II–IV) and consequently displaces H‐NS from the ftnA promoter (sites V–VI) which in turn leads to derepression of ftnA transcription. It is proposed that H‐NS binding within the ftnA promoter is facilitated by H‐NS occupation of the upstream sites through H‐NS oligomerization‐induced DNA looping. Consequently, Fur displacement of H‐NS from the upstream sites prevents cooperative H‐NS binding at the downstream sites within the promoter, thus allowing access to RNA polymerase. This direct activation of ftnA transcription by Fe2+–Fur through H‐NS antisilencing represents a new mechanism for iron‐induced gene expression.
Managerial Optimism and Corporate Finance

Considerable psychological evidence supports the existence of excessive optimism in the general population. I apply these findings to analyze some basic issues in corporate finance under the assumption that managers are excessively optimistic about the firm's prospects. A managerial optimism theory delivers empirical predictions that are highly consistent with the data, including the basic pecking order capital structure predictions that otherwise require informational asymmetries. Managerial optimism is most promising, however, as an alternative foundation for agency cost theories of corporate finance. The managerial optimism assumption aligns agency conflicts between managers and outside security holders with a well-established cognitive bias, instead of the less plausible and empirically unsupported assumption that managers knowingly destroy corporate wealth because they receive utility from empire-building. Among other things, this provides a much firmer foundation for free cash flow theories of debt.
Automated Metabolic Phenotyping of Cytochrome Polymorphisms Using PubMed Abstract Mining

Pharmacogenetics-related publications, which are increasing rapidly, provide important new pharmacogenetics knowledge. Automated approaches to extract information of new alleles and to identify their impact on metabolic phenotypes from publications are urgently needed to facilitate personalized medicine and improve clinical outcomes. Cytochrome polymorphisms, responsible for a wide variation of drug pharmacodynamics, individual efficacy and adverse effects, have significant potential for optimizing drug therapy. A few studies have addressed specialized efforts to automatically extract cytochrome polymorphisms and their characterizations regarding metabolic phenotypes from the literature. In this paper, we present a novel rule-based text-mining system to extract metabolic phenotypes of polymorphisms from PubMed abstracts with a focus on cytochrome P450. This system is promising as it achieved a precision of 85.71% in a preliminary proof-of-concept evaluation and is expected to automatically provide up-to-date metabolic information for cytochrome polymorphisms, which is critical to advance personalized medicine and improve clinical care.
Architecture of the yeast Rrp44–exosome complex suggests routes of RNA recruitment for 3′ end processing

The eukaryotic core exosome (CE) is a conserved nine-subunit protein complex important for 3′ end trimming and degradation of RNA. In yeast, the Rrp44 protein constitutively associates with the CE and provides the sole source of processive 3′-to-5′ exoribonuclease activity. Here we present EM reconstructions of the core and Rrp44-bound exosome complexes. The two-lobed Rrp44 protein binds to the RNase PH domain side of the exosome and buttresses the bottom of the exosome-processing chamber. The Rrp44 C-terminal body part containing an RNase II-type active site is anchored to the exosome through a conserved set of interactions mainly to the Rrp45 and Rrp43 subunit, whereas the Rrp44 N-terminal head part is anchored to the Rrp41 subunit and may function as a roadblock to restrict access of RNA to the active site in the body region. The Rrp44–exosome (RE) architecture suggests an active site sequestration mechanism for strict control of 3′ exoribonuclease activity in the RE complex.