gebhart/patrepeval huggingface dataset:
Albumin-linked prostate-specific antigen-activated thapsigargin- and niclosamide-based molecular grenades targeting the microenvironment in metastatic castration-resistant prostate cancer (2018)

Localized prostate cancer is curable via annihilation of the entire cancer neighborhood by surgery or local radiation. Unfortunately, once metastatic, no available therapy is curative. The vast majority will die despite aggressive systemic combinational androgen-ablation therapies. Thus, there is an urgent need for effective systemic therapeutics that sterilize the entire microenvironment in metastatic castration-resistant prostate cancer (mCRPC). To accomplish this goal, advantage can be taken of the unique biology of mCRPC cells. Like their normal cell of origin, mCRPCs retain expression of the prostate-specific differentiation protein, prostate-specific antigen (PSA), which they abundantly secrete into their extracellular fluid (ECF). This unique, and essentially universal, secretion of enzymatically active PSA into the ECF by mCRPCs creates an exploitable therapeutic index for activation of systemically delivered highly lipophilic toxins as "molecular grenades" covalently linked to cysteine-34 of human serum albumin (HSA) via a stable maleimide containing PSA cleavable peptide such that PSA-dependent hydrolysis (<i>i.e.,</i> "detonation") releases the grenades restrictively within the ECF of mCRPC. This approach decreases dose-limiting host toxicity while enhancing plasma half-life from minutes to days (<i>i.e.</i>, pharmacokinetic effect) and increasing the tissue concentration of the maleimide coupled albumin delivery (MAD) in the ECF at sites of cancer due to the enhanced permeability of albumin at these sites (<i>i.e.,</i> enhanced permeability and retention effect). This allows the MAD-PSA detonated grenades to circulate throughout the body in a non-toxic form. Only within sites of mCRPC is there a sufficiently high level of enzymatically active PSA to efficiently "pull the pin" on the grenades releasing their lipophilic cell-penetrant toxins from HSA. Thus, if a sufficient level of "detonation" occurs, this will kill mCRPC cells, and sterilize the entire PSA-rich metastatic sites via a bystander effect. In this review, two examples of such MAD-PSA detonated molecular grenades are presented-one based upon thapsigagin and the other on niclosamide.
Lactate dehydrogenase as a biomarker for early renal damage in patients with sickle cell disease (2015)

Among many complications of sickle cell disease, renal failure is the main contributor to early mortality. It is present in up to 21% of patients with sickle cell disease. Although screening for microalbuminuria and proteinuria is the current acceptable practice to detect and follow renal damage in patients with sickle cell disease, there is a crucial need for other, more sensitive biomarkers. This becomes especially true knowing that those biomarkers start to appear only after more than 60% of the kidney function is lost. The primary purpose of this study is to determine whether lactate dehydrogenase (LDH) correlates with other, direct and indirect bio-markers of renal insufficiency in patients with sickle cell disease and, therefore, could be used as a biomarker for early renal damage in patients with sickle cell disease. Fifty-five patients with an established diagnosis of sickle cell disease were recruited to in the study. Blood samples were taken and 24-h urine collection samples were collected. Using Statcrunch, a data analysis tool available on the web, we studied the correlation between LDH and other biomarkers of kidney function as well as the distribution and relationship between the variables. Regression analysis showed a significant negative correlation between serum LDH and creatinine clearance, R (correlation coefficient) = -0.44, P = 0.0008. This correlation was more significant at younger age. This study shows that in sickle cell patients LDH correlates with creatinine clearance and, therefore, LDH could serve as a biomarker to predict renal insufficiency in those patients.
A Spoofing Attack against a Cancelable Biometric Authentication Scheme (2014)

ID/password-based authentication is commonly used in network services. Some users set different ID/password pairs for different services, but other users reuse a pair of ID/password to other services. Such recycling allows the list attack in which an adversary tries to spoof a target user by using a list of IDs and passwords obtained from other system by some means (an insider attack, malwares, or even a DB leakage). As a countermeasure agains the list attack, biometric authentication attracts much attention than before. In 2012, Hattori et al. proposed a cancelable biometrics authentication scheme (fundamental scheme) based on homomorphic encryption algorithms. In the scheme, registered biometric information (template) and biometric information to compare are encrypted, and the similarity between these biometric information is computed with keeping encrypted. Only the privileged entity (a decryption center), who has a corresponding decryption key, can obtain the similarity by decrypting the encrypted similarity and judge whether they are same or not. Then, Hirano et al. showed the replay attack against this scheme, and, proposed two enhanced authentication schemes. In this paper, we propose a spoofing attack against the fundamental scheme when the feature vector, which is obtained by digitalizing the analogue biometric information, is represented as a binary coding such as Iris Code and Competitive Code. The proposed attack uses an unexpected vector as input, whose distance to all possible binary vectors is constant. Since the proposed attack is independent from the replay attack, the attack is also applicable to two revised schemes by Hirano et al. as well. Moreover, this paper also discusses possible countermeasures to the proposed spoofing attack. In fact, this paper proposes a countermeasure by detecting such unexpected vector.
Comparative phylogenomics of Streptococcus pneumoniae isolated from invasive disease and nasopharyngeal carriage from West Africans (2012)

Comparative phylogenomics of invasive and carriage S. pneumoniae isolates identified a number of putative virulence determinants that may be important in the progression of S. pneumoniae from the carriage phase to invasive disease. Virulence determinants that contribute to S. pneumoniae pathogenicity are likely to be distributed randomly throughout its genome rather than being clustered in dedicated loci or islands. Compared to other S. pneumoniae serotypes, serotype 1 appears most genetically uniform.
Diffuse Optical Tomography Imaging of the Hemodynamic Response to a Breath Hold for Use in Breast Cancer Detection (2012)

We discuss here a recent study using diffuse optical tomography to make simultaneous dual-breast measurements in 21 subjects during a respiratory challenge. An exponential fit to the transient response differentiates between tumor-bearing and healthy breasts.
Lymphadenopathy-Associated-Virus Infection and Acquired Immunodeficiency Syndrome (1986)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Application of the Novel Nalu™ Neurostimulation System for Peripheral Nerve Stimulation (2022)

Peripheral nerve stimulation is an established treatment modality for chronic neuropathic pain. Over the last decade, with the advent of innovative devices and delivery platforms, peripheral nerve stimulation has evolved from invasive open surgeries to image-guided, minimally invasive percutaneous procedures. The authors hereby present a novel device, the Nalu™ Neurostimulation System (Nalu Medical, CA, USA), which has established its advantages in providing predictable and reliable peripheral nerve stimulation therapy for chronic neuropathic pain management. This novel device is effective in treating chronic pain conditions such as post-herniorrhaphy pain syndrome, intercostal neuralgia, post-laminectomy syndrome, and complex regional pain syndrome and holds great promise for the treatment of peripheral neuropathic pain.
Selective Inhibition of Regulatory T Cells by Targeting the PI3K–Akt Pathway (2014)

Despite the strides that immunotherapy has made in mediating tumor regression, the clinical effects are often transient, and therefore more durable responses are still needed. The temporary nature of the therapy-induced immune response can be attributed to tumor immune evasion mechanisms, mainly the effect of suppressive immune cells and, in particular, regulatory T cells (Treg). Although the depletion of Tregs has been shown to be effective in enhancing immune responses, selective depletion of these suppressive cells without affecting other immune cells has not been very successful, and new agents are sought. We found that PI3K-Akt pathway inhibitors selectively inhibit Tregs with minimal effect on conventional T cells (Tconv). Our results clearly show selective in vitro inhibition of activation (as represented by a decrease in downstream signaling) and proliferation of Tregs in comparison with Tconvs when treated with different Akt and PI3K inhibitors. This effect has been observed in both human and murine CD4 T cells. In vivo treatment with these inhibitors resulted in a significant and selective reduction in Tregs in both naïve and tumor-bearing mice. Furthermore, these PI3K-Akt inhibitors led to a significant therapeutic antitumor effect, which was shown to be Treg dependent. Here, we report the use of PI3K-Akt pathway inhibitors as potent agents for the selective depletion of suppressive Tregs. We show that these inhibitors are able to enhance the antitumor immune response and are therefore promising clinical reagents for Treg depletion.
PARTITIONING OF AROMATIC MOLECULES IN AQUEOUS BIPHASIC SYSTEMS (1999)

ABSTRACT Aqueous biphasic systems (ABS) may be suitable for the separation of aromatic molecules in industrial and environmental settings; hence it is invaluable to have predictive models of partitioning behavior in these systems for design and evaluation purposes. In a continuing study of the partition of small aromatic organic molecules, the distribution of several relatively hydrophilic substituted benzene species is reported. The partitioning behavior of five charged substituted benzene species (phthalic acid, 4-hydroxybenzoic acid, benzoic acid, salicylic acid, and p-toluic acid) and one uncharged species (1,3-dinitrobenzene) has been studied in ABS prepared from stock solutions of 40% (w/w) PEG-2000 and increasing concentrations of four water-structuring salts [K3PO4, K2CO3, (NH4)2SO4, and NaOH]. Comparison has been made with published data on the partitioning of these solutes in 1-octanol/water biphasic systems. In general, the partition of these species may be understood in terms of the free energy of hydration of the salt forming the ABS and the dissociation of the charged groups of the distributed solutes.
Seeking to Understand and Address the Impacts of Biological Phosphorus Removal on Biosolids Dewatering (2013)

Seeking to Understand and Address the Impacts of Biological Phosphorus Removal on Biosolids DewateringWhile biological phosphorus removal (BPR) is becoming more common, the effect it has on solids digestion and dewatering is just now being recognized and must be confronted. This paper discusses some of the theory behind bioflocculation and dewatering of biosolids, the consequences of BPR and anaerobic digestion on dewatering, and some mitigating measures that are being considered. Amongst these...Author(s)Gary F. ShimpJames L. BarnardCharles B. BottSourceProceedings of the Water Environment FederationDocument typeConference PaperPublisherWater Environment FederationPrint publication date Oct, 2013ISSN1938-6478DOI10.2175/193864713813716309Volume / Issue2013 / 9Content sourceWEFTECCopyright2013Word count125
A case study from M.D. Anderson Cancer Center: 26-year-old female with self-palpated axillary adenopathy (2005)

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Unravelling soluble immune checkpoints in chronic lymphocytic leukemia: Physiological immunomodulators or immune dysfunction (2022)

Chronic lymphocytic leukemia (CLL) is a lymphoid neoplasm characterized by the accumulation of mature B cells. The diagnosis is established by the detection of monoclonal B lymphocytes in peripheral blood, even in early stages [monoclonal B-cell lymphocytosis (MBL<sup>hi</sup>)], and its clinical course is highly heterogeneous. In fact, there are well-characterized multiple prognostic factors that are also related to the observed genetic heterogenicity, such as immunoglobulin heavy chain variable region (IGHV) mutational status, del17p, and <i>TP53</i> mutations, among others. Moreover, a dysregulation of the immune system (innate and adaptive immunity) has been observed in CLL patients, with strong impact on immune surveillance and consequently on the onset, evolution, and therapy response. In addition, the tumor microenvironment is highly complex and heterogeneous (i.e., matrix, fibroblast, endothelial cells, and immune cells), playing a critical role in the evolution of CLL. In this study, a quantitative profile of 103 proteins (cytokines, chemokines, growth/regulatory factors, immune checkpoints, and soluble receptors) in 67 serum samples (57 CLL and 10 MBL<sup>hi</sup>) has been systematically evaluated. Also, differential profiles of soluble immune factors that discriminate between MBL<sup>hi</sup> and CLL (sCD47, sCD27, sTIMD-4, sIL-2R, and sULBP-1), disease progression (sCD48, sCD27, sArginase-1, sLAG-3, IL-4, and sIL-2R), or among profiles correlated with other prognostic factors, such as IGHV mutational status (CXCL11/I-TAC, CXCL10/IP-10, sHEVM, and sLAG-3), were deciphered. These results pave the way to explore the role of soluble immune checkpoints as a promising source of biomarkers in CLL, to provide novel insights into the immune suppression process and/or dysfunction, mostly on T cells, in combination with cellular balance disruption and microenvironment polarization leading to tumor escape.
Nouvelles stratégies d’analyse endoscopique des maladies digestives (2015)

Novel endoscopic techniques for the analysis of the digestive wall have recently been developed to allow investigating digestive diseases beyond standard "white-light" macroscopic imaging of the mucosal surface. Among innovative techniques under clinical evaluation, confocal endomicroscopy and optical frequency domain imaging (OFDI) are the most promising. Indeed, these techniques allow performing in vivo microscopy with different levels in terms of depths and magnification, as well as functional assessment of structures. Some of these techniques, such as capsule-based OFDI, are also less invasive than traditional endoscopy and might help screening large groups of patients for specific disorders, for instance oesophageal precancerous diseases. In this review, we will focus on the results obtained with these techniques in precancerous, inflammatory and neuromuscular disorders.
Mincer–Zarnowitz quantile and expectile regressions for forecast evaluations under aysmmetric loss functions (2017)

Abstract Forecasts are pervasive in all areas of applications in business and daily life. Hence evaluating the accuracy of a forecast is important for both the generators and consumers of forecasts. There are two aspects in forecast evaluation: (a) measuring the accuracy of past forecasts using some summary statistics, and (b) testing the optimality properties of the forecasts through some diagnostic tests. On measuring the accuracy of a past forecast, this paper illustrates that the summary statistics used should match the loss function that was used to generate the forecast. If there is strong evidence that an asymmetric loss function has been used in the generation of a forecast, then a summary statistic that corresponds to that asymmetric loss function should be used in assessing the accuracy of the forecast instead of the popular root mean square error or mean absolute error. On testing the optimality of the forecasts, it is demonstrated how the quantile regressions set in the prediction–realization framework of Mincer and Zarnowitz (in J. Mincer (Ed.), Economic Forecasts and Expectations: Analysis of Forecasting Behavior and Performance (pp. 14–20), 1969) can be used to recover the unknown parameter that controls the potentially asymmetric loss function used in generating the past forecasts. Finally, the prediction–realization framework is applied to the Federal Reserve's economic growth forecast and forecast sharing in a PC manufacturing supply chain. It is found that the Federal Reserve values overprediction approximately 1.5 times more costly than underprediction. It is also found that the PC manufacturer weighs positive forecast errors (under forecasts) about four times as costly as negative forecast errors (over forecasts).
Therapeutic blockade of activin-A improves NK cell function and antitumor immunity (2019)

Natural killer (NK) cells are innate lymphocytes that play a major role in immunosurveillance against tumor initiation and metastatic spread. The signals and checkpoints that regulate NK cell fitness and function in the tumor microenvironment are not well defined. Transforming growth factor-β (TGF-β) is a suppressor of NK cells that inhibits interleukin-15 (IL-15)-dependent signaling events and increases the abundance of receptors that promote tissue residency. Here, we showed that NK cells express the type I activin receptor ALK4, which, upon binding to its ligand activin-A, phosphorylated SMAD2/3 to suppress IL-15-mediated NK cell metabolism. Activin-A impaired human and mouse NK cell proliferation and reduced the production of granzyme B to impair tumor killing. Similar to TGF-β, activin-A also induced SMAD2/3 phosphorylation and stimulated NK cells to increase their cell surface expression of several markers of ILC1 cells. Activin-A also induced these changes in TGF-β receptor-deficient NK cells, suggesting that activin-A and TGF-β stimulate independent pathways that drive SMAD2/3-mediated NK cell suppression. Last, inhibition of activin-A by follistatin substantially slowed orthotopic melanoma growth in mice. These data highlight the relevance of examining TGF-β-independent SMAD2/3 signaling mechanisms as a therapeutic axis to relieve NK cell suppression and promote antitumor immunity.
Mechanism of Splicing of Unusual Intron in Human Proliferating Cell Nucleolar P120 (1999)

Abstract : The purpose of this project has been to gain a better understanding of pre-mRNA splicing mechanisms by studying SR proteins (a family of trans-acting splicing factors), exonic splicing enhancers and non-conventional splicing of AT-AC introns. AT-AC introns are a rare type of intron present in a wide variety of genes including Pl2O. High Pl2O gene expression correlates with rapid cell proliferation as in cancer cells. The goals of the proposal have been met by work in three major areas of investigation. Specific consensus exonic splicing enhancers (ESEs) for individual SR proteins, 5F2/ASF, SRp4O, SRp55 and 5C35, were identified by an in vitro SELEX procedure. Sequences matching these consensus ESEs stimulate splicing of conventional and non-conventional introns. A nonsense mutation in BRCAl, the breast cancer susceptibility gene, that is associated with familial breast and ovarian cancer causes skipping of the entire exon. This mutation is within a consensus SR protein binding site and in vitro splicing analysis showed that exon skipping is due to the failure of an SR protein, SE2/ASF, to recognize the ESE. Using in vitro splicing complementation assays, SR proteins, which are required for conventional intron splicing, were shown to be required for excision of AT-AC introns.
Thirty years of recombinant BCG: new trends for a centenary vaccine (2021)

<b>Introduction</b>: Global perception of the potential for Bacille Calmette-Guérin (BCG), and consequently recombinant BCG (rBCG), in a variety of prophylactic and therapeutic applications has been increasing. A century of information on BCG, and three decades of experience with rBCG, has generated solid knowledge in this field.<b>Area covered</b>: Here, we review the current state of knowledge of BCG and rBCG development. Molecular tools have facilitated the expression of a variety of molecules in BCG, with the aim of improving its efficacy as a tuberculosis vaccine, generating polyvalent vaccines against other pathogens, including viruses, bacteria, and parasites, and developing immunotherapy approaches against noninvasive bladder cancer. BCG's recently appraised heterologous effects and prospects for expanding its application to other diseases are also addressed.<b>Expert opinion</b>: There are high expectations for new tuberculosis vaccines currently undergoing advanced clinical trials, which could change the prospects of the field. Systems biology could reveal effective biomarkers of protection, which would greatly support vaccine development. The development of appropriate large-scale production processes would further support implementation of new vaccines and rBCG products. The next few years should consolidate the broader applications of BCG and produce insights into improvements using the recombinant BCG technology.
1D and 2D Time-Resolved Emission Measurements of Circuits Fabricated in 14 nm Technology Node (2020)

Time-Resolved Emission (TRE) measurements for circuit debugging, fault localization, and circuit characterization are discussed along with recent detectors developments that have improved their low-voltage sensitivity, while maintaining an excellent jitter and low noise performance. Advantages and disadvantages of TRE methodologies are discussed and contrasted with laser probing techniques. 14 NM test cases are presented for logic debug, SRAM characterization, and early technology development. Finally, several advanced applications that are mostly unique to TRE are summarized. TRE has a unique capability to contribute to test and diagnostics applications, especially when conditions make laser-based technique difficult to use due to its invasiveness and the lack of resolution.