(C) 2014 Elsevier Ltd. All rights reserved.”
“Comparative genomic analyses of primates offer

considerable potential to define and understand the processes that mold, shape, and transform the human genome. However, primate taxonomy is both complex and controversial, with marginal unifying consensus of the evolutionary hierarchy of extant primate species. Here we provide new genomic sequence (similar to 8 Mb) from 186 primates representing 61 (similar to 90%) of the described genera, and we include outgroup species from Dermoptera, Scandentia, and Lagomorpha. The resultant phylogeny is exceptionally robust and illuminates events in primate evolution from ancient to recent, clarifying numerous taxonomic controversies and providing new data on human evolution. Ongoing speciation, reticulate evolution, ancient relic

GSK1210151A lineages, unequal rates of evolution, and disparate distributions of insertions/deletions among the reconstructed primate lineages are uncovered. Our resolution of the primate phylogeny provides an essential evolutionary framework with far-reaching applications including: human selection and adaptation, global emergence of zoonotic diseases, mammalian comparative genomics, primate taxonomy, and conservation of endangered species.”
“Introduction: Despite recent therapeutic advances, lung cancer is a difficult disease to manage. This study assessed clinicians’ perceptions of care difficulty, quality of life (QOL), and symptom reports for their lung cancer patients compared with their patients with breast, prostate, and colon cancer.\n\nMethods: find more This report focused on secondary analyses from the Eastern Cooperative Oncology Group (ECOG) Symptom Outcomes and Practice Patterns (SOAPP) study (E2Z02); outcome measures LY294002 cost included clinician ratings of 3106 solid tumor patients. Univariate analyses focused on patterns of disease-specific perceptions; multivariable analyses examined

whether disease-specific differences persisted after covariate inclusion.\n\nResults: In univariate comparisons, clinicians rated lung cancer patients as more difficult to treat than other solid tumor patients, with poorer QOL and higher symptom reports. After covariates were adjusted, the odds of clinicians perceiving lower QOL for their lung cancer patients were 3.6 times larger than for patients with other solid tumors (odds ratio = 3.6 [95% confidence interval, 2.0-6.6]; p < 0.0001). In addition, the odds of clinicians perceiving weight difficulties for their lung cancer patients were 3.2 times larger (odds ratio = 3.2 [95% confidence interval, 1.7-6.0]; p = 0.0004). No other outcome showed significant differences between lung versus other cancers in multivariable models.\n\nConclusion: Clinicians were more pessimistic about the well-being of their lung cancer patients compared with patients with other solid tumors.

epuraeae, Urodinychidae: 123 Uroobovella pulchella (Berlese, 1904), and Macrochelidae: Glyptholaspis americana (Berlese, 1888) were recorded for the first time in the Iberian Peninsula.”
“Although cowpox virus (CPXV) infections in a variety of dead-end hosts have been investigated in Germany for more than 50 years, data on species and geographical distribution of CPXV in reservoir hosts are sparse. Here we present the first comprehensive study of 825 rodents that have been collected in Bavaria, Southern

Germany. In summary, Caspase inhibitor in vivo six different rodent species (Apodemus flavicollis, Myodes glareolus, Microtus arvalis, Apodemus sylvaticus, Microtus agrestis, and Arvicola amphibius) were trapped at three main trapping sites and investigated using a serum neutralization test (SNT). Prevalence of orthopox virus (OPV)-neutralizing antibodies was (with exception of one trapping site) highest in bank voles, ranging from 24.5% to 42.4%; often with SNT titers >=

96. Two up to 25% of yellow-necked mice were OPV sero-positive, but wood mice only at one site with 5.5%. Up to 7.7% of common voles were found to be OPV seroreactive, while M. agrestis and A. amphibius only sporadically showed seroreactivity. Further analyses of a subset of 450 bank voles and yellow-necked mice trapped at one site over a 18-month period revealed that male yellow-necked mice and female gravid yellow-necked mice had significantly more OPV-neutralizing KPT-8602 cost antibodies. Mean body weight and OPV-seroreactivity were significantly negatively associated in male A. flavicollis. This was not due to shorter body length or smaller body mass index, but previously OPV-infected male A. flavicollis had dramatically reduced mean kidney 3-deazaneplanocin A concentration weights. Seroreactivity in female bank voles was positively related to lung weights. We also found that both male yellow-necked mice and male bank voles with positive SNT titers had higher infestation rates with ectoparasites.

We here show for the first time that A. flavicollis beside M. glareolus is a hypothetic host for CPXV, and that there are big geographical and spatial variations concerning the seroprevalence in rodent populations in South Germany.”
“In light of the increasing interest in the development of functional food, several researches have focused on the production of food grade emulsifiers of nutritional interest, especially enriched in the eicosapentaenoic (EPA) and docosahexaenoic acids (DHA). The aim of this paper is to make a review of the production of monoacylglycerols (MAG) and diacylglycerols (DAG) obtained from different feedstock, mainly fish oil. A section of this paper is dedicated to the raw materials used as feedstock for these emulsifiers production. The health benefits of these partial acylglycerols are outlined.

Induction of miR396

results in inhibition of cell proliferation, and this outcome is independent of the UV-B photoreceptor UV resistance locus 8, as well as ATM AND RAD3-RELATED and the mitogen-activated protein kinase MPK6, but is dependent on MPK3. Transgenic plants expressing an artificial target mimic directed against miR396 (MIM396) with a decrease in the endogenous microRNA SCH727965 price activity or plants expressing miR396-resistant copies of several GRFs are less sensitive to this inhibition. Consequently, at intensities that can induce DNA damage in Arabidopsis plants, UV-B radiation limits leaf growth by inhibiting cell division in proliferating tissues, a process mediated by miR396 and GRFs.”
“The medicinal plant Pelargonium sidoides is fast becoming threatened due to the

overharvest of its tubers from the wild to produce a phytopharmaceutical for treating respiratory infections. The action of the coumarins is implicated in the efficacy of the commercial herbal extract with the highly oxygenated coumarins exhibiting the best anti-bacterial and anti-viral activity. Through this work we aimed at exploring the metabolic effects of 4 Agrobacterium rhizogenes transformation. After confirmation of transgenesis using PCR amplification of the rol A (320bp), rol B (400bp) and rol C (600bp) genes, metabolite profiles indicated a high level of GSK1210151A chemical structure variability between the different transgenic clones but these had more compounds compared to non-transgenic control cultures. This was represented by a two- to four-fold increase in detected metabolites in transgenic clones. We quantified several commercially

important coumarins, flavonoids and p38 protein kinase phenolic acids. One of the clones had six out of nine of these metabolites. Overall, the concentration of these metabolites of interest were significantly changed in transgenic root cultures, for instance shikimic acid was recorded at the highest level in clone A4T-A. Production of key metabolites at significantly higher concentrations due to transgenesis and positive anti-bacterial activity exhibited by transgenic roots lends support to the idea of developing these clones as an alternative source that will allow for sustainable access to economically valuable secondary compounds of P. sidoides. (C) 2010 Elsevier Inc. All rights reserved.”
“Health statistics of Mongolia indicate that hospital-acquired infections (HAIs) occur in 0.01-0.05% of all hospital admissions. This is considerably lower than internationally reported rates. A one-day survey was conducted in two tertiary hospitals of Ulaanbaatar in September 2008 to estimate HAI prevalence, associated risk factors and patterns of antibiotic usage. Among 933 patients surveyed, 50 (5.4%) were diagnosed with HAI. Prevalence of surgical site infection was 1.1% (3.9% among surgical patients), bloodstream infection 0.3%, respiratory tract infection 1.

Human Rh C glycoprotein (RhCG) forms a 4 trimeric complex that plays an essential role in ammonia excretion and renal pH regulation. The X-ray crystallographic structure of human RhCG, determined at 2.1 angstrom resolution, reveals the mechanism of ammonia transport. Each monomer contains 12 transmembrane

helices, one more than in the bacterial homologs. Reconstituted into proteoliposomes, RhCG conducts NH(3) to raise internal pH. Models of the erythrocyte Rh complex based on our RhCG structure suggest that the erythrocytic Rh complex is composed of stochastically assembled heterotrimers of RhAG, RhD, and RhCE.”
“Recently, interest on the role of the renin-angiotensin system (RAS) in the pathophysiology of Selleck Ganetespib hypertension has shifted toward greater emphasis on new developments in local RAS in specific tissues. We have focused our recent investigations on the role of the intrarenal-intratubular RAS in hypertension. All of the components needed for angiotensin II generation are present within the various compartments in the kidney. This brief review is focused on recent evidence that inappropriate activation of renin in distal nephron segments, by acting on angiotensinogen generated in the proximal

tubule cells and delivered to the distal nephron may contribute to increased distal intrarenal angiotensin II formation, KU-57788 nmr sodium retention, and development and progression of hypertension. J Am Soc Hypertens 2009;3(2):96-104. (C) 2009 American Society of Hypertension. All rights reserved.”
“Root rot of papaya, caused by Phytophthora parasitica var. nicotianae, is the most widespread and important disease of papaya and is particularly damaging to many papaya varieties popular in southern India, such as Coorg Honey Dew and Surya. The objective of this study was to evaluate biocontrol agents (BCAs) under controlled check details and field conditions for their efficacy against Phytophthora infecting papaya cv. Surya and to detect and quantify the reduction in the pathogen population by immunological techniques. Glomus mosseae, Trichoderma harzianum and Pseudomonas

fluorescens were inoculated at the time of planting in the nursery and at the time of transplanting in single, dual and tripartite combinations allowing colonization up to 90 days. Plants were challenged thereafter with Phytophthora inoculum multiplied on specialized Phytophthora medium. Uninoculated plants and those inoculated with pathogen only were controls. All the BCAs in general improved plant growth and reduced severity of disease compared to uninoculated control in both pot experiments and under field conditions. Plants preinoculated with G. mosseae + T. harzianum, provided the best results when challenged with Phytophthora, with increased plant height, girth and yield and also reduced disease severity over plants not inoculated with BCAs.

\n\nResults: The four leading symptoms were fatigue (96%), fever (86%), cough (81%), and dyspnea (79%). No significant differences in symptom prevalence were found between different sexes, ages, performance statuses, ward locations, or selleck chemicals llc underlying diseases, except for fewer episodes of

dizziness, more frequent episodes of cough in patients older than 80 years, and more episodes of jaundice in ward service subjects. Only the presence of abdominal distension differed significantly between surviving and deceased patients (22.9% vs. 40.3%; p = 0.004). After the start of palliative care, patients’ DNR consent increased (105/115 before, 114/115 after). Patients’ recognition of the diagnosis and prognosis increased from 13 to 64, respectively, with a simultaneous increase in family members’ recognition (66 before, 114 after).\n\nConclusion: Hospice care with good symptom control is warranted for patients

with late-stage nonmalignant disease who need appropriate 3 end-of-life care. Medical personnel need education in the importance of palliative care and the identification of patients who could Vorinostat inhibitor benefit from it. In addition, patients should be informed of its availability. Copyright (C) 2012, Elsevier Taiwan LLC & Formosan Medical Association. All rights reserved.”
“Approximately 20-30% of patients with gastro-oesophageal reflux symptoms report inadequate symptom relief while on PPI therapy Persisting acid or non-acid reflux can be demonstrated in 40-50% of them suggesting that there is room for anti-reflux therapy in these patients New anti-reflux compounds

aim at decreasing the occurrence of transient lower oesophageal sphincter relaxations (TLOSRs) which represent the main mechanism of all types of reflux The most promising classes of compounds are GABA(B) agonists and mGluR5 antagonists which have been shown to reduce both reflux episodes and symptoms and are currently under evaluation in phase II and III clinical trials Compounds that target TLOSR activity represent a promising new therapeutic option for patients who suffer from GORD symptoms These drugs will probably be developed as add-on therapy in combination with PPIs provided the tolerability and safety issues are resolved (C) 2010 Elsevier Ltd All rights reserved”
“In case of Zenker’s diverticulum, treatment is indicated as soon AZD7762 research buy as the diagnosis is established. Therapy should aim at the elimination of dysphagia and the symptoms of food retention and should reliably prevent recurrence. Currently, three different therapeutic approaches are applied: the classical option is open transcervical myotomy and diverticulectomy/diverticulopexy and alternatively stapled diverticulostomy with a linear stapler or flexible endoscopic diverticulostomy is propagated. As compared to the surgical (open) approach, rigid or flexible endotherapy is less invasive. However, endotherapy is not always feasible for all types of Zenker’s diverticulum and the recurrence rate is high.

aeolicus FlgM protein exhibits alpha-helical character in circular dichroism (CD) experiments, though the percentage of alpha-helical content decreases with increased

temperature, consistent with the FlgM assuming a less folded conformation. We also show that the A. aeolicus FlgM exhibits cooperativity in chemical denaturation experiments, consistent with a globular nature. Furthermore, we use the fluorescent probe FlAsH to Selleck PLX4032 show that the H2 helix is ordered, even in the unbound state and that the H1 and H2 helices appear to be associated with each other in the absence of the sigma(28) protein. Finally, we demonstrate that the H2 helix assumes an extended conformation at 85 degrees C. Based on our results, we propose that at 20 degrees C the A. aeolicus FlgM assumes a four-helix bundle-like conformation that becomes a more extended conformation at the A. aeolicus’ physiological temperature of 85 degrees C. (C) 2010 Elsevier B.V. All rights reserved.”
“Four species of Prunella L. (Prunella vulgaris L., ML323 chemical structure Prunella laciniata L., Prunella grand:flora L. and Prunella orientalis Bornm.)

belong to the family of Lamiaceae and representing popular Western and Chinese herbal medicine were examined for the content of phenolic compounds. Phenolic acids (rosmarinic acid, caffeic acid, ferulic acid, chlorogenic acid, protocatechuic acid), flavonoids (rutin, quercetin) in different quantitative proportions depending on extracts were determined by the rapid, selective and accurate method combining solvent/acid hydrolysis LY3023414 purchase extraction and high performance liquid chromatographydiode array detection (HPLC-DAD). Water, methanol, butanol, acetonitrile, ethyl acetate, hexane and their acidic

solutions were used to examine the efficiency of different solvent systems for the extraction of phenolic compounds. Acid hydrolysis extraction was established as the most suitable extraction method for phenolic compounds. (C) 2011 Elsevier B.V. All rights reserved.”
“The antioxidant activity of the aqueous ethanolic extract of doum leaves, Hyphaene thebaica L. (Palmae) was studied. Data obtained showed that the extract can inhibit reactive oxygen species attack on salicylic acid (IC(50) = 1602 mu g/ml) in a dose dependant manner using xanthine/hypoxanthine oxidase assay. Four major flavonoidal compounds were identified by LC/SEI as; Quercetin glucoside, Kaempferol rhamnoglucoside and Dimethyoxyquercetin rhamnoglucoside.

“
“Due to the high importance of biofilms on river ecosystems, assessment of pesticides’ adverse effects is necessary

but is impaired www.selleckchem.com/products/ldc000067.html by high variability and poor reproducibility of both natural biofilms and those developed in the laboratory. We constructed a model biofilm to evaluate the effects of pesticides, consisting in cultured microbial strains, Pedobacter sp. 7-11, Aquaspirillum sp. T-5, Stenotrophomonas sp. 3-7, Achnanthes minutissima N71, Nitzschia palea N489, and/or Cyclotella meneghiniana N803. Microbial cell numbers, esterase activity, chlorophyll-a content, and the community structure of the model biofilm were examined and found to be useful as biological factors for evaluating the pesticide effects. The model biofilm was formed through the cooperative interaction of bacteria and diatoms, and a preliminary experiment using the herbicide atrazine, which inhibits diatom

growth, indicated that the adverse effect on diatoms Sapitinib inhibited indirectly the bacterial growth and activity and, thus, the formation of the model biofilm. Toxicological tests using model biofilms could be useful for evaluating the pesticide effects and complementary to studies on actual river biofilms.”
“The increasing occurrence of drug-resistant bacterial infections in the clinic has created a need for new antibacterial agents. Natural products have historically been a rich source of both antibiotics and lead compounds for new antibacterial agents. The natural product simocyclinone D8 (SD8) has been reported to inhibit DNA gyrase, a validated antibacterial drug target,

by a unique catalytic inhibition mechanism of action. In this work, we have prepared simplified flavone-based analogues inspired by the complex natural product and evaluated their inhibitory activity and mechanism of action. While two of these compounds do inhibit DNA gyrase, they do so by a different mechanism of action than SD8, namely DNA intercalation. (C) 2013 Elsevier Ltd. All rights reserved.”
“In explicitly correlated coupled-cluster singles and doubles [CCSD(F12)] calculations, the basis set incompleteness error in the double excitations is reduced to such an extent that the error in HDAC inhibitor the Hartree-Fock energy and the error in the single excitations become important. Using arguments from perturbation theory to systematically truncate the coupled-cluster singles and CCSD(F12) Lagrangians, a series of coupled-cluster models are proposed and studied that reduce these basis set incompleteness errors through additional single excitations into a complementary auxiliary basis. Convergence with model and size of complementary basis is rapid and there appears to be no need to go beyond second-order models. Our iterative second-order approach is a slight improvement over the existing noniterative approach, but its main advantage is that it is suitable for response theory.

5 FPS and 15 FPS groups for DCA (3.4 +/- 2.0 min vs. 4.0 +/- 4.7 min; p = 0.42) and PCI (11.9 +/- 8.4

min vs. 13.3 +/- 9.7 min; p = 0.57), respectively. Conclusions Fluoroscopy at 7.5 FPS, compared with 15 FPS, is a simple and effective method in reducing operator and patient radiation dose during TRA DCA and PCI. (C) 2014 by the American College of Cardiology Foundation”
“Short-chain aliphatic esters are small volatile molecules that produce fruity and pleasant aromas and flavors. Most of these esters are artificially produced or extracted from natural sources at high cost. It is, however, possible to ‘naturally’ produce these molecules using biocatalysts such as lipases and esterases. NSC 750424 A gene coding for a newly uncovered lipase was isolated from a previous metagenomic study and cloned into E. coli BL21 (DE3) for overexpression using the pET16b plasmid. Using this recombinant strain as a whole-cell

biocatalyst, short chain esters were efficiently synthesized by transesterification and esterification reactions in organic media. The recombinant lipase (LipIAF5-2) showed good affinity toward glyceryl trioctanoate and the highest conversion yields were obtained for the transesterification of glyceryl triacetate with methanol. Using a simple cetyl-trimethylammonium bromide pretreatment increased the synthetic activity by a six-fold factor and the whole-cell biocatalyst Y-27632 mechanism of action showed the highest activity at 40 degrees C with a relatively high water content of 10% (w/w). The whole-cell biocatalyst showed excellent tolerance to alcohol and short-chain fatty acid denaturation. Substrate affinity was equally effective

with all primary alcohols tested as acyl acceptors, with a slight preference for methanol. The best transesterification conversion of 50 mmol glyceryl triacetate Ferroptosis inhibitor drugs into isoamyl acetate (banana fragrance) provided near 100% yield after 24 hours using 10% biocatalyst loading (w/w) in a fluidized bed reactor, allowing recycling of the biocatalyst up to five times. These results show promising potential for an industrial approach aimed at the biosynthesis of short-chain esters, namely for natural flavor and fragrance production in micro-aqueous media.”
“With the rising prevalence of antimicrobial resistance, the failure rate of the standard triple therapy for Helicobacter pylori infection is increasing. Sequential therapy and concomitant therapy have been recommended to replace standard triple therapy for H. pylori eradication in regions with high clarithromycin resistance. The aim of this prospective, randomized, and controlled study was to simultaneously assess the efficacies of 10-day sequential and 7-day concomitant therapies versus a 7-day standard triple therapy for treating H. pylori infection. Consecutive H.

These results will assist in the design of small molecules for inhibiting oral BoNT intoxication and of delivery vehicles for oral administration of biologics.”
“This study was designed to identify genes that regulate the transition from FSH- to LH-dependent development in

the bovine dominant follicle (DF). Serial analysis of gene expression (SAGE) was used to compare the transcriptome of granulosa cells isolated from the most oestrogenic growing cohort follicle (COH), the newly selected DF and its largest subordinate follicle (SF) which is destined for atresia. Follicle diameter, follicular fluid oestradiol (E) and E:progesterone ratio confirmed follicle identity. Results show that there are 93 transcript species differentially expressed in DF granulosa cells, but only LY3023414 price 8 of these encode proteins known to be involved in DF development. Most characterised transcripts upregulated in the DF are from tissue development genes that regulate selleck products cell differentiation, proliferation, apoptosis, signalling and tissue remodelling. Semiquantitative real-time

PCR analysis confirmed seven genes with upregulated (P <= 0.05) mRNA expression in DF compared with both COH and SF granulosa cells. Thus, the new genes identified by SAGE and real-time PCR, which show enhanced mRNA expression in the DF, may regulate proliferation (cyclin D2; CCND2), prevention of apoptosis or DNA damage (growth arrest and DNA damage-inducible, beta; GADD45B), RNA synthesis (splicing factor, arginine/serine rich 9; SFRS9) and unknown processes associated with enhanced steroidogenesis

(ovary-specific acidic protein; DQ004742) in granulosa cells of DF at the onset of LH-dependent development. Further studies are required to show whether the expression of identified genes is dysregulated when abnormalities occur during DF selection or subsequent development.”
“BackgroundDelayed gastric emptying (GE) is common in patients with severe burns. This study was designed to investigate effects and mechanisms of electroacupuncture (EA) on gastric motility in rats with burns.\n\nMethodsMale rats (intact and vagotomized) were implanted with gastric electrodes, chest and abdominal wall electrodes for investigating selleck kinase inhibitor the effects of EA at ST-36 (stomach-36 or Zusanli) on GE, gastric slow waves, autonomic functions, and plasma interleukin 6 (IL-6) 6 and 24h post severe burns.\n\nKey Results(i) Burn delayed GE (P<0.001). Electroacupuncture improved GE 6 and 24h post burn (P<0.001). Vagotomy blocked the EA effect on GE. (ii) Electroacupuncture improved burn-induced gastric dysrhythmia. The percentage of normal slow waves was increased with EA 6 and 24h post burn (P=0.02). (iii) Electroacupuncture increased vagal activity assessed by the spectral analysis of heart rate variability (HRV). The high-frequency component reflecting vagal component was increased with EA 6 (P=0.004) and 24h post burn (P=0.03, vs sham-EA).

For example, oleanolic acid, betulin or betulinic acid are more cytotoxic with a pronounced activity for tumor cells. GA, however, is easily to earn, cheap and shows apoptotic effects on tumor cells – like the other triterpenoic acids. These facts bring GA and derivatives in the focus of our scientific interest. Here we tried to improve the poor

cytotoxicity of GA by simple derivatization. Thus, we selected various glutamyl and aspartyl substituents for the synthesis of C(3) esters of GA methyl ester. A short (3-5 steps) synthesis was elaborated that allowed to access more effective compounds. One compound, methyl 30 3-(0-benzyl-L-glutamyl)-11-oxo-olean-12-en-30-oate (5), having a glutamyl substituent with a benzyl protected side chain showed up to 67-fold higher cytoxicity and an up to 140-fold better selectivity towards tumor JQEZ5 mw cells than parent GA. All compounds were evaluated by a sulforhodamine B assay as well as by

a trypan blue test and extra acridine orange/ethidium bromide tests for apoptosis.”
“The C5 and C6 sugars generated from sweet sorghum bagasse pretreated with five different chemical or physical schemes and then further hydrolyzed with a fibrolytic cocktail were determined. Hydrolysates were fermented with three yeast strains in order to determine which combination generated the highest amount of bioethanol. The bagasse only treated with the enzyme complex generated 50% of the total C5 and C6 sugars available. The pressure-cooked selleck chemical and extruded pretreatments further hydrolyzed with the enzymes generated 17% more sugars compared to the enzyme alone treatment. The enzyme increased the total sugar content

in approximately 40% in the three acid pretreated hydrolysates. STI571 in vitro Among the different pretreatments, only the extrusion process did not generate inhibitors acetic acid, furfural and 5-hydroxymethylfurfural. At 24 h fermentation, the strains Saccharomyces cerevisiae and Issatchenkia orientalis produced, respectively 183.9 and 209.2 mg ethanol/g dry bagasse previously treated with HCl and enzymes. (C) 2013 Elsevier Ltd. All rights reserved.”
“The claim that Grote-Hynes theory (GHT), when it provides accurate rates, is equivalent to multidimensional variational transition state theory (VTST) has been debated for decades with convincing arguments on both sides. For the two theories to be equivalent a perfect dividing surface with no recrossing must exist. We describe an easily implemented test employing deterministic microcanonical (NVE) trajectories which can identify situations where no perfect dividing surface exists and thereby potentially falsify the claim of equivalence. We use this test to reach data-supported conclusions about the relationship between GHT and VTST. (C) 2014 AIP Publishing LLC.”
“Epidermal growth factor receptor (EGFR)-targeted therapies have been effective in some cancers, but not in hepatocellular carcinoma (HCC).