gebhart/patrepeval huggingface dataset:
Accelerated disappearance of ovarian follicles in mid-life: implications for forecasting menopause (1992)

Menopause is triggered by the number of ovarian follicles falling below a threshold number and is irreversible because oogonial stem cells disappear after birth. Since it is the result of programmed disappearance of a limited store of follicles, menopause can be predicted using mathematical models based on total follicle counts at different ages. Our model shows follicle numbers decline bi-exponentially rather than as a simple exponential function of age, as had been assumed, with a first exponential rate parameter of -0.097 and a second of -0.237. The change occurred when numbers had fallen to the critical figure of 25,000 at age 37.5 years. The unexpectedly faster rate of ovarian ageing afterwards lowers the follicle population to 1000 at approximately 51 years, and was adopted as the menopausal threshold because it corresponds to the median age of menopause in the general population. Had the earlier rate persisted menopause would not be expected until 71 years. The impact of step reductions of follicle numbers on the prospective span of menstrual life was predicted by the model. A reduction by 50% before age 30 years resulted in the threshold being reached at 44 years and 0.6 year later for every subsequent year until age 37.5 years after which it is reached at 48 years. A reduction of 90% in childhood before age 14 years could result in menopause as early as 27 years, with increments of 0.6 year per year afterwards until after 37.5 years when it is expected at age 41 years.(ABSTRACT TRUNCATED AT 250 WORDS)
Simple time-domain optical method for estimating the depth and concentration of a fluorescent inclusion in a turbid medium (2004)

A simple time-domain optical method for estimating the depth and concentration of fluorescent inclusions in turbid media is described. We demonstrate direct depth estimation of a localized fluorescent object from the temporal position of the temporal point-spread function maximum. The depth estimation permits recovery of the fluorophore concentration, both of which are essential quantities for optical molecular imaging studies. Since the maximum is independent of the fluorophore concentration, excitation laser power, detector gain, and other system-dependent factors, this method ensures a robust and efficient approach.
Analysis of Vibroarthrographic Signals for Knee Osteoarthritis Diagnosis (2012)

Osteoarthritis (OA) is the most common joint disease, except for the X-ray diagnosis of knee lesions, not more invasive detection methods. Clinical examination of the physician for long-term degenerative arthritis patients, found the knee often with crepitus sound in range of motion, but this is a subjective feeling, can't be recorded and a comparative analysis. in this study, knee sound signal is obtained by an innovative stethoscope device with goniometer. the sound signal is input to personal computer and segmented according to goniometer data. Fourier transform of signal is done. Power spectrum is obtained and partition index calculated. Distribution parameters are obtained and optimum classification threshold then decided. Assess the VGA signal and compare knee OA with the X-ray image, and the VAG characteristics signal function using with mean, variance, skew ness and kurtosis statistics function analysis accuracy. Our total accuracy up to 82.69% showed good sensitivity and specificity rate. Vibroarthrographic signals of knee provide an economic alternative to x-ray examination for osteoarthritis patients.
SMOTE: Synthetic Minority Over-sampling Technique (2002)

An approach to the construction of classifiers from imbalanced datasets is described. A dataset is imbalanced if the classification categories are not approximately equally represented. Often real-world data sets are predominately composed of ``normal'' examples with only a small percentage of ``abnormal'' or ``interesting'' examples. It is also the case that the cost of misclassifying an abnormal (interesting) example as a normal example is often much higher than the cost of the reverse error. Under-sampling of the majority (normal) class has been proposed as a good means of increasing the sensitivity of a classifier to the minority class. This paper shows that a combination of our method of over-sampling the minority (abnormal) class and under-sampling the majority (normal) class can achieve better classifier performance (in ROC space) than only under-sampling the majority class. This paper also shows that a combination of our method of over-sampling the minority class and under-sampling the majority class can achieve better classifier performance (in ROC space) than varying the loss ratios in Ripper or class priors in Naive Bayes. Our method of over-sampling the minority class involves creating synthetic minority class examples. Experiments are performed using C4.5, Ripper and a Naive Bayes classifier. The method is evaluated using the area under the Receiver Operating Characteristic curve (AUC) and the ROC convex hull strategy.
Abstract 1789: Auristatin-based antibody-drug conjugates are synergistic in combination with PI3K-AKT-mTOR pathway inhibitors in hematologic malignancies and carcinoma (2011)

Abstract Antibody-drug conjugates (ADCs) that couple the potent anti-mitotic agents monomethyl auristatin E or F (MMAE or MMAF) to tumor antigen specific monoclonal antibodies have demonstrated antitumor activity in preclinical models. We report that the combination of auristatin-based ADCs with inhibitors of the phosphoinositide 3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) signaling pathway improves cytotoxic activity in Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), and renal cell carcinoma (RCC) cell line models. Implicated in tumor cell growth and survival, the PI3K-AKT-mTOR pathway is frequently hyperactivated in carcinomas and hematologic malignancies with elevated AKT activity reported in ∼64% of Hodgkin Reed-Sternberg (HRS) cells and 25-52% of primary patient diffuse large B-cell lymphomas. We produced dose response curves for auristatin ADCs and PI3K-AKT-mTOR pathway inhibitors, alone and in combination, and then performed combination index (CI) analysis using the Chou-Talalay method. The CD30-targeting ADC brentuximab vedotin (SGN-35) and the CD19-targeting ADC (SGN-19A) were synergistic (CI &amp;lt; 0.7) with the allosteric mTORC1 inhibitors sirolimus and temsirolimus in panel of lymphoma cell lines. Similarly, a CD70 targeting ADC (SGN-75) was synergistic with sirolimus and temsirolimus in RCC cell lines. Unconjugated MMAE drug was synergistic in combination with sirolimus and temsirolimus, proving the auristatin component of the ADC is responsible for enhanced combinatorial activity. Next, we found that brentuximab vedotin, SGN-19A, and SGN-75 were each synergistic with NVP-BEZ235, a dual specificity PI3K and mTORC1/2 catalytic site inhibitor. Therefore, the synergy observed with auristatin ADCs is generalizable to inhibitors of the PI3K-AKT-mTOR pathway and not unique to rapamycin analogs. Finally, the brentuximab vedotin combination with temsirolimus was evaluated in a L428 mouse xenograft model of B-like HL. Temsirolimus and brentuximab vedotin alone showed antitumor activity in the L428 model; however, the brentuximab vedotin plus temsirolimus combination had significantly greater (P-value = 0.001) antitumor activity than either drug alone. The mechanism for the synergy observed in these combinations may involve reduced expression of antiapoptotic proteins by mTOR pathway inhibitors, which sensitizes cancer cells to auristatin ADCs. Collectively, these data suggest the potential for auristatin ADC plus mTOR inhibitor cotherapy in PI3K-AKT-mTOR pathway hyperactivated lymphomas and carcinomas. 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 1789. doi:10.1158/1538-7445.AM2011-1789
Protease-Activated Drug Development (2012)

In this extensive review, we elucidate the importance of proteases and their role in drug development in various diseases with an emphasis on cancer. First, key proteases are introduced along with their function in disease progression. Next, we link these proteases as targets for the development of prodrugs and provide clinical examples of protease-activatable prodrugs. Finally, we provide significant design considerations needed for the development of the next generation protease-targeted and protease-activatable prodrugs.
Adjuvant Therapy With Fluorouracil and Oxaliplatin in Stage II and Elderly Patients (between ages 70 and 75 years) With Colon Cancer: Subgroup Analyses of the Multicenter International Study of Oxaliplatin, Fluorouracil, and Leucovorin in the Adjuvant Treatment of Colon Cancer Trial (2012)

The results of these subset analyses show no statistically significant benefit (OS and DFS) for the addition of oxaliplatin to FL as adjuvant treatment for either stage II and elderly patients.
BMPR2 mutations found in Japanese patients with familial and sporadic primary pulmonary hypertension (2004)

Primary pulmonary hypertension (PPH) is a potentially lethal disorder, in which heterozygous mutations within the bone morphogenetic protein type II receptor (BMPR2) gene (BMPR2) have been identified. We conducted a molecular study of BMPR2 mutations in 4 Japanese families with familial PPH and 30 Japanese patients with sporadic PPH, and found 13 different mutations, of which 10 were novel, including missense (n=2), nonsense (n=4), frameshift (n=3), and splice-donor site (n=1) mutations. In total, BMPR2 mutations were found in all 4 familial PPH cases and 12 (40%) of the sporadic PPH cases. Further, a majority of the mutations found were predicted to cause premature termination, as previously reported. In the 9 mutations found in the sporadic cases, 2 were shown to be de novo, 2 were shared in multiple cases, 1 was shared with an FPPH case, and 1 was the same as previously reported in Caucasian FPPH. These results indicate that a substantial portion of Japanese PPH patients carry BMPR2 mutations with considerable heterogeneity.
The effect of stem cell proliferation regulators demonstrated with an in vitro assay (1988)

Spleen colony formation after transplantation of bone marrow cells into irradiated mice has been used as an assay for hematopoietic stem cells (CFU-S), but has serious limitations intrinsic to an in vivo assay. In this report we describe experiments using an in vitro clonogenic assay that is especially suitable for studies of stem cell regulation as defined growth factors and normal untreated bone marrow can be used. We have demonstrated that the colony-forming cells have proliferative properties in common with CFU-S and respond to specific proliferation regulators previously detected using the spleen colony assay.
Ruthenium Complex-Catalyzed Silylation of Olefins. Selective Synthesis of Allylsilanes (1988)

Abstract (1-2; 5-6-η-Cyclooctadiene)(1-6-η-cyclooctatriene)ruthenium catalyzes the silylation of olefins at 60–140 °C to give allylsilanes with good selectivity in high yields. The reactions of trialkylsilane with 2-methyl-1-butene, 2-methyl-2-butene, and 3-methyl-1-butene give the same product, 3-methyl-1-trialkylsilyl-2-butene. Silylation of ethyl (E)-2-butenoate gives ethyl (E)-4-trialkylsilyl-2-butenoate in high yield.
Effective organization and visualization of web search results (2006)

While searching the web, the user is often confronted by a great number of results, generally displayed in a list which is sorted according to the relevance of the results. Facing the limits of this approach, we propose to explore new organizations and presentations of search results, as well as new types of interactions with the results to make their exploration more intuitive and efficient. The main topic of this paper is the processing of the results coming from an information retrieval system. Although the relevance depends on the results quality, the effectiveness of the results processing represents an alternative way to improve the relevance for the user. Given the current expectations, this processing is composed by an organization step and a visualization step. Then the proposed approach organizes the results according to their meaning using a Kohonen Self-Organizing Map (SOM), and visualizes them in a 3D scene to increase the representation space. The 3D metaphor proposed here is a city.
Lysosomal Membrane Permeabilization Induces Cell Death in a Mitochondrion-dependent Fashion (2003)

A number of diseases are due to lysosomal destabilization, which results in damaging cell loss. To investigate the mechanisms of lysosomal cell death, we characterized the cytotoxic action of two widely used quinolone antibiotics: ciprofloxacin (CPX) or norfloxacin (NFX). CPX or NFX plus UV light (NFX*) induce lysosomal membrane permeabilization (LMP), as detected by the release of cathepsins from lysosomes. Inhibition of the lysosomal accumulation of CPX or NFX suppresses their capacity to induce LMP and to kill cells. CPX- or NFX-triggered LMP results in caspase-independent cell death, with hallmarks of apoptosis such as chromatin condensation and phosphatidylserine exposure on the plasma membrane. LMP triggers mitochondrial membrane permeabilization (MMP), as detected by the release of cytochrome c. Both CPX and NFX* cause Bax and Bak to adopt their apoptotic conformation and to insert into mitochondrial membranes. Bax-/- Bak-/- double knockout cells fail to undergo MMP and cell death in response to CPX- or NFX-induced LMP. The single knockout of Bax or Bak (but not Bid) or the transfection-enforced expression of mitochondrion-targeted (but not endoplasmic reticulum-targeted) Bcl-2 conferred protection against CPX (but not NFX*)-induced MMP and death. Altogether, our data indicate that mitochondria are indispensable for cell death initiated by lysosomal destabilization.
Intravitreal Ceftazidime in a Rabbit Model: Dose- and Time-Dependent Toxicity and Pharmacokinetic Analysis (1987)

We delineated the dose-and time-dependent retinal toxicity of intravitreal ceftazidime using electroretinography (ERG) in phakic rabbit eyes. Toxicity was evaluated following intravitreal doses ranging from 0.5 to 50 mg/0.1 ml. Eyes were examined prior to injection, at one day, and at seven days after injection. ERG patterns at one and seven days indicated a toxic response to doses of 20 to 50 mg. Doses of 10 mg or less gave a transient depression of the B-wave at one day, but a return to normal was observed at the seven-day evaluation. Pharmacokinetic analysis following intravitreal injection of 2 mg of ceftazidime into uninfected phakic rabbit eyes disclosed vitreous levels of: 1711 micrograms/ml at 0 hr; 1340 micrograms/ml at 8 hr; 451 micrograms/ml at 24 hr; 270 micrograms/ml at 48 hr and 67 micrograms/ml at 72 hr. Peak aqueous humor level was 139 micrograms/ml 8 hr post-injection. Potentially therapeutic drug levels were obtained in the aqueous and vitreous humors following a nontoxic intravitreal dose of ceftazidime in a rabbit model.
Reduced Transaminase B (IlvE) Activity Caused by the Lack ofyjgFIs Dependent on the Status of Threonine Deaminase (IlvA) inSalmonella entericaSerovar Typhimurium (2004)

The YjgF/YER057c/UK114 family is a highly conserved class of proteins that is represented in the three domains of life. Thus far, a biochemical function demonstrated for these proteins in vivo or in vitro has yet to be defined. In several organisms, strains lacking a YjgF homolog have a defect in branched-chain amino acid biosynthesis. This study probes the connection between yjgF and isoleucine biosynthesis in Salmonella enterica. In strains lacking yjgF the specific activity of transaminase B, catalyzing the last step in the synthesis of isoleucine, was reduced. In the absence of yjgF, transaminase B activity could be restored by inhibiting threonine deaminase, the first enzymatic step in isoleucine biosynthesis. Strains lacking yjgF showed an increased sensitivity to sulfometruron methyl, a potent inhibitor of acetolactate synthase. Based on work described here and structural reports in the literature, we suggest a working model in which YjgF has a role in protecting the cell from toxic effects of imbalanced ketoacid pools.
DNA Binding and Cleavage by a Cationic Manganese Porphyrin−Peptide Nucleic Acid Conjugate (1997)

A cationic manganese porphyrin-peptide nucleic acid (PNA) conjugate has been prepared and used to cleave a double-stranded DNA target. Cleavage experiments were performed with a 247-base pair restriction DNA fragment containing a 10-base pair homopurine binding target for the PNA. Oxidative activation by this Mn porphyrin-PNA conjugate leads to sequence specific, 3'-staggered cleavage of both DNA strands near the strand displacement junction. Furthermore, the Mn porphyrin-PNA porphyrin conjugates bind over 100-fold better to double-stranded DNA compared to the native PNA.
Biochemical Evidence for the Oligomeric Arrangement of Bovine Rotavirus Nucleocapsid Protein and Its Possible Significance in the Immunogenicity of This Protein (1987)

The nucleocapsid protein of bovine rotavirus was shown to exist in trimeric units in both the virus particle and in infected cells, with the subunits linked by non-covalent interactions. These trimeric units complex further by disulphide bridges into larger units which may represent the hexameric structures observed by electron microscopy. Visualization of various nucleocapsid protein complexes was also achieved on polyacrylamide gels by treating virus preparations with urea at 37 degrees C or boiling in the presence and absence of 2-mercaptoethanol. Since virus particles devoid of nucleic acid were also broken down into trimeric subunits by such treatments, assembly of virus particles appears not to require an RNA-protein interaction. Four nucleocapsid-specific monoclonal antibodies with low neutralizing ability reacted with the monomeric (45,000 mol. wt., 45K), dimeric (90K), trimeric (135K) and trimeric pair (270K) subunits, indicating that a site responsible for neutralization is probably exposed after assembly of these subunits. Analysis of radiolabelled virus revealed that a high proportion (80%) of infectious particles could be immunoprecipitated by these monoclonal antibodies, suggesting that the virus particles are either partially double-shelled or have the nucleocapsid exposed on the surface. The monoclonal antibodies also cross-reacted with the nucleocapsid proteins of simian (SA11), pig (OSU), bovine (NCDV and UK) and human (Wa and ST4) rotaviruses in an immunoblot ELISA reaction. Since these six viruses belong to two different subgroups, it is likely that the antibodies did not recognize the subgroup-specific site, but a shared exposed antigenic determinant. Due to the hexameric configuration of the nucleocapsid in virus particles the neutralizing epitope may be repeatedly presented and, therefore, may contribute to the immunogenicity of this protein.
RET/PTC Rearrangements Are Associated with Elevated Postoperative TSH Levels and Multifocal Lesions in Papillary Thyroid Cancer without Concomitant Thyroid Benign Disease (2016)

RET/PTC rearrangements, resulting in aberrant activity of the RET protein tyrosine kinase receptor, occur exclusively in papillary thyroid cancer (PTC). In this study, we examined the association between RET/PTC rearrangements and thyroid hormone homeostasis, and explored whether concomitant diseases such as nodular goiter and Hashimoto's thyroiditis influenced this association. A total of 114 patients diagnosed with PTC were enrolled in this study. Thyroid hormone levels, clinicopathological parameters and lifestyle were obtained through medical records and surgical pathology reports. RET/PTC rearrangements were detected using TaqMan RT-PCR and validated by direct sequencing. No RET/PTC rearrangements were detected in benign thyroid tissues. RET/PTC rearrangements were detected in 23.68% (27/114) of PTC tissues. No association between thyroid function, clinicopathological parameters and lifestyle was observed either in total thyroid cancer patients or the subgroup of patients with concomitant disease. In the subgroup of PTC patients without concomitant disease, RET/PTC rearrangement was associated with multifocal cancer (P = 0.018). RET/PTC rearrangement was also correlated with higher TSH levels at one month post-surgery (P = 0.037). Based on likelihood-ratio regression analysis, the RET/PTC-positive PTC cases showed an increased risk of multifocal cancers in the thyroid gland (OR = 5.57, 95% CI, 1.39-22.33). Our findings suggest that concomitant diseases such as nodular goiter and Hashimoto's thyroiditis in PTC may be a confounding factor when examining the effects of RET/PTC rearrangements. Excluding the potential effect of this confounding factor showed that RET/PTC may confer an increased risk for the development of multifocal cancers in the thyroid gland. Aberrantly increased post-operative levels of TSH were also associated with RET/PTC rearrangement. Together, our data provides useful information for the treatment of papillary thyroid cancer.
Dynamic programming: The next step (2015)

We fill two gaps in the literature. First, we give a comprehensive set of equivalences allowing reordering of grouping with non-inner joins. Second, we show how to incorporate the optimal placement of grouping into a state-of-the-art dynamic programming (DP)-based plan generator.
Pressure-Induced Metal-to-Insulator Phase Transitions in the Organic Conductor (2,5 DM-DCNQI) 2 Cu (1988)

International audience
Observations of birefringence in tissues from optic-fibre-based optical coherence tomography (2002)

This paper addresses whether conventional fibre-based optical coherence tomography (OCT) is capable of obtaining birefringence information of well-organized tissues. For this purpose, a highly organized tissue, pig tendon, is studied by the use of the conventional fibre-based OCT systems. It is found that the tendons result in well-defined banded OCT images. The observed bands in the OCT images are sensitive to the wavelength of light source applied and phase retardation. The results demonstrate that conventional OCT can be used to monitor the tissue birefringence.
Enhanced two-beam coupling in colloids of ferroelectric nanoparticles in liquid crystals (2007)

We report on the first, to the best of our knowledge, studies of photorefraction in nematic liquid crystal (LC) doped with nanoferroelectric particles. We found the strong enhancement of two-beam coupling in the colloid of ferroelectric nanoparticles in LC. The effect originated from an increased birefringence of the colloid and a stronger LC reorientation torque. Our measurements allowed us to suggest that increased birefringence is caused by the contribution of polarizability anisotropy of the ferroelectric particles. Stronger reorientation torque is caused by the permanent dipole moment of the particles contributing to the dielectric anisotropy of the colloid εacol. The enhancement of two-beam coupling in LCs by doping with ferroelectric nanoparticles at extremely small concentration shows the strong potential of ferroelectric nanoparticles for improving the optical response of LCs, especially for those materials where a method of chemical synthesis has reached its limit.