gebhart/patrepeval huggingface dataset:
245 Cord blood CD34+ stem cells are efficiently transduced with anti-CD19-CAR and expanded and differentiated into viveNK™ natural killer cells which display selective cytotoxicity against B-cell leukemia (2022)

<h3>Background</h3> Chimeric antigen receptor (CAR)-engineered Natural Killer (NK) cells are a highly promising option for adoptive cancer immunotherapy. Glycostem Therapeutics has developed a closed, automated, and feeder-free system for ex vivo expansion and differentiation of umbilical cord blood-derived CD34<sup>+</sup> stem cells into highly functional NK cells, currently evaluated in a Phase I/II clinical study (ClinicalTrials.gov ID: NCT04632316). The introduction of a genetic engineering step during early culture stages makes the system suitable for CAR-NK products, for the generation of billions of off-the-shelf viveNK™ cells for antigen-directed tumor targeting. <h3>Methods</h3> To enhance the ability of NK therapies to kill resistant B-cell leukemia cells, we generated anti-CD19-CAR viveNK™ cells via lentiviral transduction with multiple second- and third-generation CARs carrying different hinge, transmembrane and intracellular domains. CAR cassettes were cloned into Glycostem’s own clinically suitable lentiviral transfer plasmid; promoter analysis identified MNDU3 as the optimal transgene driver. <h3>Results</h3> Engineered cells showed high expansion potential and fast differentiation into functional NK cells expressing specific surface markers. CAR surface expression increased up to 83% (n=8 donors) with higher Multiplicity of Infection (MOI) in a range of 1-20, but was sustained even at low (&lt;5) MOI. CAR transgene genome integration (Vector Copy Number) and transcriptional efficiency was evaluated via quantitative Polymerase Chain Reaction (PCR). Exposure of CD19-viveNK™ cells to antigen-expressing B-cell leukemia cell lines resulted in increased degranulation and very potent antigen-specific cytotoxicity. Additionally, inherent innate NK cell phenotype and responses and the mechanism of action driving CD19-CAR viveNK™ cytotoxicity were investigated via flow cytometry-based analysis and single-cell RNA-sequencing (scRNA-Seq) of CAR-transduced vs non-transduced donors. <h3>Conclusions</h3> Our data show how off-the-shelf, highly functional, and antigen-directed CAR-NK cells can be generated ex vivo, offering an option to target cancers which are often resistant or difficult to treat with standard immunotherapy.
Ethical Issues in Avian Veterinary Practice (2008)

served to galvanize veterinarians' concern with truly ethical issues.1,2 In particular, one of us (B. R.) has raised question of whether, in situations in which duties conflict, veterinarians are primarily obligated to owners (what B. R. calls the Garage Mechanic Model) or to animals (what he calls the Pediatrician Model). Beginning in 1970s, society has developed an ever-increasing concern for welfare of animals used by humans. Such issues affect all areas of veterinary medicine, from food animal to laboratory animal, to companion animal and avian practice. Although humans have kept captive birds for thousands of years, this practice was overwhelmingly utilitarian; these animals were kept for specific practical purposes. Some birds were kept for food or eggs (poultry, ducks, quail), others for hunting (falcons), still others as alarms (guinea fowl, peacocks), and others as living ornaments or for purposes of entertainment. However, as has been case with other animals, notably dogs and cats but not limited to them, companion animals have come to be valued for their own
Inappropriate benzodiazepine use in older adults and the risk of fracture (2008)

These findings suggest that inappropriate benzodiazepine use according to the Beers criteria is not associated with increased risk of fracture. Daily dose and longer duration of use (>14 days) is associated with higher risk of fracture, irrespective of the type of benzodiazepine prescribed.
Delayed-Onset Hypothesis of Antipsychotic Action (2003)

This analysis rejects the commonly held hypothesis that antipsychotic response is delayed. Rather, these findings suggest that the antipsychotic response starts in the first week of treatment and accumulates over time. Furthermore, greater improvement occurs in the first 2 treatment weeks than in the subsequent 2 treatment weeks. Proposed mechanisms of action of antipsychotic drugs need to account for this early-onset antipsychotic effect.
Mobile Phone Flashlight‐Excited Red Afterglow Bioimaging (2022)

Organic room temperature phosphorescence (RTP) materials with ultralong lifetime possess the remarkable advantage in bioimaging for elimination of background noise by characteristic time scale. However, most of RTP luminogens need to be excited by the harmful ultraviolet (UV) lamp, and exhibit green or yellow emission with shallow tissue penetration, constraining the in vivo bioimaging for further application in clinical diagnosis and pathological study. In this text, the much safer excitation process by sunlight and mobile phone flashlight is realized by organic luminogens with various electronic pull-push systems. Moreover, the bright red RTP emission with lifetime up to 344 ms is achieved by optimizing molecular geometry and electronic property. Especially, the mobile phone flashlight-excited red afterglow imaging of lymph nodes in living mice has been realized for the first time, affording a safe and conventional approach to achieve the afterglow imaging of living mice with deep issue penetration and high signal-to-noise ratios.
A new approach for the synthesis of 3-substituted cytotoxic nor-&#946;-lapachones (2013)

Several studies have demonstrated the cytotoxic potential of nor-β-lapachone derivative against cancer cells. Considering nor-β-lapachone as an important prototype, a set of new 3-substituted nor-β-lapachones was synthesized by a new synthetic route that involves the use of synthetic intermediate generated for coupling with several nucleophiles containing the carbohydrate and 2H-pyrazole substituent moieties. All the compounds were screened against four tumor cell lines. Two of the compounds showed moderate cytotoxicity, while the other compounds strongly inhibit all tested cancer cell lines.
A VLSI Optimised Parallel Tree Search for MIMO (2006)

Multiple input-multiple output (MIMO) systems are of great interest due to their ability to significantly increase the capacity of wireless communications systems, but for these to be useful they must also be practical for implementation in very large scale integrated (VLSI) circuits. A particularly difficult part of these systems is the detector, where the maximum-likelihood (ML) solution cannot be directly implemented due to its exponential complexity. Lattice decoders, such as the sphere search, exhibit near-ML performance with reduced complexity, but their application is still limited by computational requirements. Here, a number of optimisations are presented, designed to reduce the computational cost of the sphere search in the context of VLSI implementation for MIMO applications. We also propose parallel implementation strategies for such a detector, suitable for implementation in VLSI. This is then combined with a single-pass tree search approach and it is demonstrated that it can be designed so that the error-rate performance is not significantly impaired
New potent STS inhibitors based on fluorinated 4-(1-phenyl-1H-[1,2,3]triazol-4-yl)-phenyl sulfamates (2019)

A series of fluorinated analogs based on the frameworks of 4-(1-phenyl-1<i>H</i>-[1,2,3]triazol-4-yl)-phenyl sulfamates have been synthesized as steroid sulfatase (STS) inhibitors. The design of chemical structures of new potential STS inhibitors was supported by molecular docking techniques to identify potential interactions between inhibitors and amino acid residues located in the STS active site. The STS inhibitory potency was evaluated on STS isolated from human placenta. We found that compounds substituted with fluorine atom at the <i>meta</i> position demonstrated the highest inhibitory effects in enzymatic STS assay. The most active analog <b>12e</b> - inhibited STS enzyme with the IC<sub>50</sub> value of 36 nM.
A synthesis of biological invasion hypotheses associated with the introduction–naturalisation–invasion continuum (2023)

With the advent of the Anthropocene, biological invasions have reached an unprecedented level, and the number of species introductions is still increasing in an ever‐changing world. Despite major advances in invasion science, significant debate and lack of clarity remain surrounding the determinants of success of introduced species, the magnitude and dimensions of their impact, and the mechanisms sustaining successful invasions. Empirical studies show divergent impacts of alien populations on ecosystems and contrasting effects of biotic and abiotic factors on the dynamics of alien populations, which hinders the creation of a unified theory of biological invasions. Compounding these issues is the plethora of hypotheses that aim to explain invasion success, which can be unclear and contradictory. We propose a synthesis that categorizes hypotheses along a timeline of invasion. We sorted invasion hypotheses along the invasion timeline, and considered population, community and ecosystem levels. This temporal sorting of invasion concepts shows that each is relevant at a specific stage of the invasion. Although concepts and empirical findings on alien species may appear contradictory, when mapped onto an invasion timeline, they may be combined in a complementary way. An overall scheme is proposed to summarise the theoretical dynamics of ecosystems subjected to invasions. For any given case study, this framework provides a guide through the maze of theories and should help choose the appropriate concepts according to the stage of invasion.
Topic Discussion before Class——An Effective Way in Oral English Teaching (2006)

地方院校非英语专业学生英语基础较薄弱,如何消除他们不敢参与口语活动的惧怕心理,使他们开口讲英语,是大学英语教师长期思考的问题.本文从调查分析学生对于课堂教学中几种不同教学模式的反应入手,认为教师在课前提供话题,让学生围绕话题讨论的口语教学模式是一种在基础薄弱的学生中开展口语教学的有效模式.
The preparation of o-, m-, and p-alkoxy- and -phenoxy-methylbenzy chlorides (1954)

F. G. Mann and F. H. C. Stewart, J. Chem. Soc., 1954, 2819 DOI: 10.1039/JR9540002819
Comprehensive assessment of cytochromes P450 and transporter genetics with endoxifen concentration during tamoxifen treatment (2017)

Our results further support a minor contribution of CYP2C9 genetic variability toward steady-state endoxifen concentrations. Integration of clinician and genetic variables into individualized tamoxifen dosing algorithms would marginally improve their accuracy and potentially enhance tamoxifen treatment outcomes.
A randomized phase II trial comparing chemoimmunotherapy with or without bevacizumab in previously untreated patients with chronic lymphocytic leukemia (2016)

Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor (VEGF) with in vitro pro-apoptotic and antiangiogenic effects on chronic lymphocytic leukemia (CLL) cells. As monotherapy in patients with CLL, it has no clinical activity. Here we report the results of an open-label, randomized phase II trial comparing the combination of pentostatin, cyclophosphamide and rituximab (PCR) either without or with bevacizumab (PCR-B) in previously untreated CLL patients. A total of 65 evaluable patients were enrolled, 32 receiving PCR and 33 PCR-B. A higher rate of grade 3-4 cardiovascular toxicity was observed with PCR-B (33% vs. 3%, p < 0.003). Patients treated with PCR-B had a trend for a higher complete remission (CR) rate (54.5% vs 31.3%; p = 0.08), longer progression-free survival (PFS)(p = 0.06) and treatment-free survival (TFS)(p = 0.09). No differences in PFS and TFS by IGHV mutational status were observed with the addition of bevacizumab. A significant post-treatment increase in VEGF levels was observed in the PCR-B arm (29.77 to 57.05 pg/mL); in the PCR-B arm, lower baseline CCL-3 levels were significantly associated with achievement of CR (p = 0.01). In conclusion, the addition of bevacizumab to chemoimmunotherapy in CLL is generally well-tolerated and appears to prolong PFS and TFS.
Causal Laws and Effective Strategies (1979)

There are at least two kinds of laws of nature: laws of association and causal laws.1 Laws of association are the faimilar laws with which philosophers usually deal. These laws tell how often two qualities or quantities are co-associated. They may be either deterministic-the association is universal-or probabilistic. equations of physics are a good example: whenever the force on a classical particle of mass m is f the acceleration isf/m. Laws of association may be time indexed, as in the probabilistic laws of Mendelian genetics, but apart from the asymmetries imposed by time indexing, these laws are causally neutral. They tell how often two qualities co-occur; but they provide no account of what makes things happen. Causal laws, by contrast, have the word cause-or some causal surrogate, right in them. Smoking causes lung cancer; perspiration attracts wood ticks; or,-for an example from physics, force causes change in motion: to quote Einstein and Infeld ([5]: 9), The action of an external force changes the velocity... such a force either increases or decreases the velocity according to whether it acts in the direction of motion or in the opposite direction. Bertrand Russell [9] argued that laws of association are all the laws there are, and that causal principles cannot be derived from the causally symmetric laws of association. I shall here argue in support of Russell's second claim, but against the first. Causal principles cannot be reduced to laws of association; but they cannot be done away with. argument in support of causal laws relies on some facts about strategies. They are illustrated in a letter which I recently received from TIAA-CREF, a company which provides insurance for college teachers. letter begins:
RED EDGE EXCITATION EFFECT IN INTACT EYE LENS (1989)

Shift in the wavelength of emission upon shift in the excitation wavelength towards the red edge of the absorption band is termed Red Edge Excitation Shift (REES). This effect is observed only in situation where the fluorophore mobility with respect to the surrounding matrix is considerably reduced. We have observed such red edge excitation effect in the intact eye lens. The REES observed for a normal lens is different from that seen in a photodamaged lens and hence appears to be a potential tool to monitor the changes in the state of the lens. Photodamage experiments with tryptophan in polyethylene glycol (PEG) and intact eye lens indicate that the red edge photon can also cause photodamage.
An error-entropy minimization algorithm for supervised training of nonlinear adaptive systems (2002)

The paper investigates error-entropy-minimization in adaptive systems training. We prove the equivalence between minimization of error's Renyi (1970) entropy of order /spl alpha/ and minimization of a Csiszar (1981) distance measure between the densities of desired and system outputs. A nonparametric estimator for Renyi's entropy is presented, and it is shown that the global minimum of this estimator is the same as the actual entropy. The performance of the error-entropy-minimization criterion is compared with mean-square-error-minimization in the short-term prediction of a chaotic time series and in nonlinear system identification.
Paralog-specific signaling by IRAK1/4 maintains MyD88-independent functions in MDS/AML (2023)

Dysregulation of innate immune signaling is a hallmark of hematologic malignancies. Recent therapeutic efforts to subvert aberrant innate immune signaling in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) have focused on the kinase IRAK4. IRAK4 inhibitors have achieved promising, though moderate, responses in preclinical studies and clinical trials for MDS and AML. The reasons underlying the limited responses to IRAK4 inhibitors remain unknown. In this study, we reveal that inhibiting IRAK4 in leukemic cells elicits functional complementation and compensation by its paralog, IRAK1. Using genetic approaches, we demonstrate that cotargeting IRAK1 and IRAK4 is required to suppress leukemic stem/progenitor cell (LSPC) function and induce differentiation in cell lines and patient-derived cells. Although IRAK1 and IRAK4 are presumed to function primarily downstream of the proximal adapter MyD88, we found that complementary and compensatory IRAK1 and IRAK4 dependencies in MDS/AML occur via noncanonical MyD88-independent pathways. Genomic and proteomic analyses revealed that IRAK1 and IRAK4 preserve the undifferentiated state of MDS/AML LSPCs by coordinating a network of pathways, including ones that converge on the polycomb repressive complex 2 complex and JAK-STAT signaling. To translate these findings, we implemented a structure-based design of a potent and selective dual IRAK1 and IRAK4 inhibitor KME-2780. MDS/AML cell lines and patient-derived samples showed significant suppression of LSPCs in xenograft and in vitro studies when treated with KME-2780 as compared with selective IRAK4 inhibitors. Our results provide a mechanistic basis and rationale for cotargeting IRAK1 and IRAK4 for the treatment of cancers, including MDS/AML.
A preliminary investigation of exhaled breath from patients with celiac disease using selected ion flow tube mass spectrometry. (2010)

Our data suggest that breath alcohol levels are unlikely to be of diagnostic use in CD, although further investigation of those recently diagnosed with the disorder may be warranted.
Ultrasonic Measurements in Particle Size Analysis (2000)

Abstract The particle size distribution and concentration of a colloidal dispersion can be determined by measuring its ultrasonic velocity and/or attenuation coefficient as a function of frequency and then using a suitable mathematical model to interpret the spectra. Ultrasonic spectroscopy can be used to analyze particle sizes between about 10 nm and 1000 µm, and is suitable for application to concentrated systems (often up to 50 wt%). This technique has considerable advantages over many alternative technologies because it can be applied to systems that are optically opaque without the need of any sample preparation.
An ethical hierarchy for decision making during medical emergencies (2010)

Evidence from well-designed clinical trials may guide clinicians, reduce regional variation, and lead to improved outcomes. Many physicians choose to ignore evidence-based practice guidelines. Using unproven therapies outside of a randomized trial slows recruitment in clinical trials that could yield information on clinical and economic efficacy. Using acute stroke therapy as an illustration, we present an ethical hierarchy for therapeutic decision making during medical emergencies. First, physicians should offer standard care. If no standard care option exists, the physician should consider enrollment in a randomized clinical trial. If no trial is appropriate, the physician should consider a nonrandomized registry, or consensus-based guidelines. Finally, only after considering the first 3 options, the physician should use best judgment based on previous personal experience and any published case series or anecdotes. Given the paucity of quality randomized clinical trial data for most medical decisions, the "best judgment" option will be used most frequently. Nevertheless, such a hierarchy is needed because of the limited time during medical emergencies for consideration of general principles of clinical decision making. There should be general agreement in advance as to the hierarchy to follow in selecting treatment for critically ill patients. Were more clinicians to follow this hierarchy, and choose to participate in clinical trials, the generation of new knowledge would accelerate, yielding rigorous data supporting or refuting the efficacy and safety of new interventions more quickly, thus benefiting far more patients over time.
Germination and accumulation of metabolites in legume seedlings grown under salt stress (2019)

The effects of salinity on the physiological behavior of seeds, leaves and stems of five legumes were evaluated to identify early criteria for selection of salt-tolerant plant species. Four levels of salinity (0, 50, 100 and 200 mM NaCl) were tested. After 4 weeks, three sets of 7 plants were taken from each culture medium to evaluate the lipid, protein and proline contents. Thus, the NaCl supply resulted in a significant decrease in the contents
	in lipids and germination rate in all species studied. However, this depressive effect of salt was more marked in the two sensitive glycophytes (Phaseolus vulgaris and Glycine max); their germination rate being greatly slowed down from 3 g / l of NaCl with critical thresholds of inhibition to germination at 9 and 12 g / l of NaCl respectively. However, this critical threshold was above 21 g / l for
	Mucuna poggei (optional halophyte), Phaseolus adenanthus (halophyte) and Vigna unguiculata (moderately tolerant glycophyte). The depressive effect of salt was less marked on stem height growth in P. adenanthus, M. poggei and V. unguiculata except in the latter two species at 200 mM. Salt intake resulted in protein and proline accumulation in the leaves of M. poggei, P. 
	adenanthus and V. unguiculata compared with G. max and P. vulgaris. Germination rate and protein accumulation and leaf proline could be used as early criteria for selection of salinity tolerant legumes.
	In vitro, the effects of NaCl concentrations on physiological behavior of seeds, leaves and stems of five leguminous plants were evaluated. Plants were submitted to 4 levels of salt stress at the roots (0, 50, 100 and 200 mM NaCl). After four weeks, lipids, proteins and proline are randomly sampled
	plants. Results showed that sodium chloride had an undergoing effect on growth of stems and seed germination of the species studied. The germination rates of Glycine max and Phaseolus vulgaris (sensitive glycophytes) were affected from 3 g / l of NaCl, with critical thresholds at 9 and 12 g / l respectively. In contrast, critical thresholds with Mucuna poggei (optional halophyte), Vigna unguiculata (moderately tolerant glycophyte) and P. adanthus (natural halophyte) were found to be above 21 g / l. The reduction of
	In this study, we observed that mutagenesis was observed in M. poggei and V. unguiculata this inhibition was observed when nutrient solutions were enriched with 200 mM. The lipid content was reduced in all the species, and was significantly increased in the tolerant species (M. poggei, P. adanthus, and V. unguiculata). In contrast, proteins and leaf proline were negatively affected by salt concentration to G. max and P. vulgaris. Seed germination, proteins and proline could be used as physiological criteria for salt tolerant leguminous plants